用于制备抗肿瘤沙粒病毒的方法以及沙粒病毒突变体
文献发布时间:2023-06-19 11:27:38
本申请要求于2018年9月12日提交的德国专利申请DE102018215551.8的优先权权益,其内容在此全文引入作为参考用于所有目的。
本发明涉及用于制备抗肿瘤沙粒病毒的方法,沙粒病毒突变体,分离的蛋白或肽(特别是分离的糖蛋白),沙粒病毒和编码相应蛋白或肽的核酸。
沙粒病毒属于人致病性多形RNA病毒家族。具有这些病毒的疾病属于人畜共患疾病,因为动物、主要是啮齿类动物是它们的天然宿主。人畜共患疾病是可以从动物传播到人的疾病,反之亦然。
已知至少8种沙粒病毒在人中引起疾病,典型地,引起无菌性脑膜炎和出血热。可在人中引起疾病的已知病毒为淋巴细胞性脉络丛脑膜炎病毒(LCMV)、瓜纳里托病毒(GTOV)、胡宁病毒(JUNV)、拉沙病毒(LASV)、卢约病毒(LUJV)、马丘波病毒(MACV)、萨比埃病毒(SABV)和怀特沃特阿罗约病毒(WWAV)。
哺乳动物沙粒病毒属的沙粒病毒分为两大类,旧大陆沙粒病毒和新大陆沙粒病毒。这两大类在地理分布上和遗传学上是不同的。旧大陆沙粒病毒,如淋巴细胞性脉络丛脑膜炎病毒主要在东半球的国家(如欧洲、亚洲和非洲的国家)发现。相比之下,新大陆沙粒病毒已经在西半球的国家(如阿根廷、玻利维亚、委内瑞拉、巴西和美国)发现。
沙粒病毒在细胞中复制并作为病毒颗粒(感染性颗粒)进入胞外间隙。病毒颗粒多形,常为圆形,其直径主要为110nm-130nm,最高达50nm-300nm。病毒颗粒的衣壳被包膜蛋白包围,所述包膜蛋白由双脂质膜和突出成刺状的糖蛋白(GP1和GP2)的同源三聚体构成。GP1朝向外,并在感染过程中与细胞受体结合。GP2朝向相反并介导与细胞的融合。Z-蛋白在脂质层下面如环状排列,位于核壳内的核糖核蛋白(RNP)-复合物各由较短RNA片段(S片段3.5kb)、较长RNA片段(L片段7.2kb)和核蛋白组成。L-蛋白(病毒聚合酶)与所述RNP复合物相关。L-和S-片段携带遗传信息并各自编码两种蛋白质。单链RNA具有混合极性(即双义),序列(约19-30bp)在其3'非翻译端是保守的,在病毒家族中该处也是保守的。首先核蛋白和L-蛋白的mRNA被转录,接着是复制和Z-蛋白和糖蛋白前体的mRNA转录,最后是病毒蛋白的翻译和修饰。
沙粒病毒作为疫苗接种载体的用途是众所周知的。一个突出的例子是用于抗阿根廷出血热的疫苗接种病毒Candid#1。它是胡宁病毒的疫苗接种变体。
从WO2009/083210A1已知复制缺陷的(即基因修饰的)沙粒病毒颗粒(病毒颗粒)尤其是在用于治疗肿瘤疾病的用途,例如黑色素瘤、前列腺癌、乳腺癌和肺癌。文献“Development of replication-defective lymphocytic choriomeningtitis virusvectors for the induction of potent CD8+ T cell immunity”(Nature Medicine,vol.16,no.3,2010年3月,p.339-345;doi:10.1038/nm.214)提到了用于这种病毒颗粒癌症免疫治疗的潜在应用领域。
另外从WO2006/008074A1已知产生逆转录病毒并具有沙粒病毒糖蛋白假型病毒颗粒的包装细胞用于实体瘤的基因治疗的用途。
上述用于肿瘤治疗的现有技术的方法基于使用通过基因工程非常复杂才产生的病毒颗粒。此外,对基因治疗疗法而言,用基因工程病毒颗粒或产生病毒颗粒的包装细胞对肿瘤组织进行充分的、治疗有效的转导通常是不可实现的。
然而,从WO2016/166285A1已知用于治疗和/或预防肿瘤的沙粒病毒,其中,所述沙粒病毒不含基因组外源RNA。另外,从WO2016/166285A1已知一种用于具有肿瘤消退性能的沙粒病毒的生产方法。
然而,仍然需要用于治疗和/或预防肿瘤的特异性的、特别是治疗有效的沙粒病毒。
本发明的基本目的是生产具有抗肿瘤性能和/或改善的抗肿瘤性能的沙粒病毒。此外,本发明的基本目的是提供相应的沙粒病毒突变体、分离的蛋白或肽(特别是糖蛋白和/或L-蛋白)以及编码它们的核酸。
上述目的通过根据独立权利要求1的淋巴细胞性脉络丛脑膜炎病毒突变体、根据独立权利要求15的方法、根据权利要求22的淋巴细胞性脉络丛脑膜炎病毒突变体、根据权利要求26的药剂或药物组合物、根据权利要求28的分离的蛋白或肽以及根据权利要求29的分离的核酸来解决。所述方法和所述淋巴细胞性脉络丛脑膜炎病毒突变体的优选实施方案是从属权利要求的主题并受本说明书的限定。本发明的其它方面在说明书中公开。所有权利要求的措词由此通过明确引用本说明书的内容并入本文。
本发明基于这样令人惊讶的发现,即与野生型病毒相比,沙粒病毒、特别是淋巴细胞性脉络丛脑膜炎病毒(LCMV)的某些突变体可以具有改善的抗肿瘤活性。
因此,本发明大体上涉及一种淋巴细胞性脉络丛脑膜炎病毒的突变体,优选毒株WE的突变体。
与野生型淋巴细胞性脉络丛脑膜炎病毒株WE相比,所述突变体可以能够在肿瘤细胞如H1975细胞、HCC1954细胞、鼠胰腺癌细胞或人黑色素瘤细胞中进行更强的繁殖。与LCMV-WE野生型相比,所述突变体还可以能够在体内诱导更强的天然免疫激活。与LCMV-WE野生型相比,所述突变体还可以能够具有更强的体内抗肿瘤作用。与LCMV-WE野生型相比,所述突变体还可以能够增加肿瘤特异性CD8+ T细胞的扩增。所述突变体还可以能够增强肿瘤特异性CD8+ T细胞的功能。与LCMV-WE野生型相比,所述突变体也可以具有更强的刺激肿瘤特异性T细胞的能力。
本发明所述的淋巴细胞性脉络丛脑膜炎病毒突变体优选包含编码糖蛋白的核酸,其中所述糖蛋白在对应于SEQ ID NO:10所示野生型糖蛋白序列的181和185位的位置包含至少一个突变。与SEQ ID NO:10所示野生型糖蛋白序列和/或由所述核酸编码的相应蛋白相比,优选的突变是Arg185→Trp和/或Ile181→Met(例如仅Arg185→Trp、仅Ile181→Met或Arg185→Trp和Ile181→Met)。虽然本申请的实施例证明任意一个所述突变的存在可能已经足以提供比野生型淋巴细胞性脉络丛脑膜炎病毒改善的功能,但所列举的两种突变同时存在将进一步改善LCMV的功能,这种改善作用可以是叠加的或甚至是协同的。因此,在优选的实施方案中,两种突变都存在于本发明的LCMV中。
不希望受理论的约束,进一步认为,与其它突变的存在、特别是与LCMV的其它基因或蛋白中其它突变的存在无关,糖蛋白中一个或两个上述突变的存在可改善LCMV的功能(例如,如上所述的在肿瘤细胞中的复制或繁殖、抗肿瘤活性和/或免疫系统刺激)。该假设基于这样的发现,即糖蛋白中所述的突变Arg185→Trp和Ile181→Met保持保守,而一些其它突变在连续传代期间出现和消失,和/或在不同突变株中是不保守的。该假设还基于这样的事实,即LCMV的糖蛋白在病毒颗粒包膜上形成突刺,因此被认为在病毒感染肿瘤细胞的能力中起主要作用。
本发明所述的LCMV突变体可以包含编码糖蛋白的核酸,其中所述糖蛋白与SEQ IDNO:10所示野生型糖蛋白序列具有至少约95%、优选至少约96%、优选至少约97%、优选至少约98%、优选至少约99%、优选至少约99.1%、优选至少约99.2%、优选至少约99.3%、优选至少约99.4%、优选至少约99.5%、优选至少约99.6%、优选至少约99.7%的序列同一性,和/或可以包含由所述核酸编码的相应蛋白。
本发明所述的LCMV突变体可以包含编码糖蛋白的核酸,其中,与SEQ ID NO:10所示野生型糖蛋白相比,所述糖蛋白包含突变Arg185→Trp和Ile181→Met。
本发明所述的LCMV突变体可以包含编码糖蛋白的核酸,其中所述糖蛋白与SEQ IDNO:18、26、34、42、50和58中任一个所示序列具有至少约95%、优选至少约96%、优选至少约97%、优选至少约98%、优选至少约99%、优选至少约99.1%、优选至少约99.2%、优选至少约99.3%、优选至少约99.4%、优选至少约99.5%、优选至少约99.5%、优选至少约99.7%的序列同一性,或者优选相同,和/或可以包含由所述核酸编码的相应蛋白。
本发明所述的LCMV突变体可以包含编码糖蛋白的核酸,其中所述核酸包含与SEQID NO:17、25、33、41、49和57所示序列具有至少约95%、优选至少约96%、优选至少约97%、优选至少约98%、优选至少约99%、优选至少约99.1%、优选至少约99.2%、优选至少约99.3%、优选至少约99.4%、优选至少约99.5%、优选至少约99.6%、优选至少约99.7%的序列同一性,或者优选相同,和/或可以包含由所述核酸编码的相应蛋白。
如上所述,据信在病毒颗粒包膜上形成突刺的LCMV糖蛋白在病毒感染肿瘤细胞的能力中起主要作用。然而,其它蛋白质优选被呈递于LCMV中。
本发明所述的LCMV突变体可以包含编码L-蛋白的核酸,所述L-蛋白与SEQ ID NO:16所示野生型L-蛋白序列具有至少约95%、优选至少约96%、优选至少约97%、优选至少约98%、优选至少约99%、优选至少约99.1%、优选至少约99.2%、优选至少约99.3%、优选至少约99.4%、优选至少约99.5%、优选至少约99.6%、优选至少约99.7%的序列同一性,和/或可以包含由所述核酸编码的相应蛋白。
本发明所述的LCMV突变体可以包含编码L-蛋白的核酸,其中所述L-蛋白与SEQ IDNO:24、32、40、48、56和64中任一个所示序列具有至少约95%、优选至少约96%、优选至少约97%、优选至少约98%、优选至少约99%、优选至少约99.1%、优选至少约99.2%、优选至少约99.3%、优选至少约99.4%、优选至少约99.5%、优选至少约99.6%、优选至少约99.7%、优选至少约99.8%、优选至少约99.9%的序列同一性,或优选相同,和/或可以包含由所述核酸编码的相应蛋白。
本发明所述的LCMV突变体可以包含编码L-蛋白的核酸,其中所述L-蛋白在对应于SEQ ID NO:16所示野生型L-蛋白序列的253、1512、1513、1758、1995、2094、2115、2141、2175和2185位的位置包含1、2、3、4、5、6、7、8、9或10个突变。与SEQ ID NO:16所示野生型L-蛋白序列相比,这些位置突变的优选实施方案是:Lys253→Arg;Lys1512→Met;Lys1513→Glu;Ser1758→Phe;Phe1995→Ser;Ile2094→Val;Lys2115→Glu;Thr2141→Ala;Arg2175→Lys;Thr2185→Ala,和/或可以包含由所述核酸编码的相应蛋白。优选地,所述LCMV突变蛋白包含前述突变中的1、2、3、4或5个。
本发明所述的LCMV突变体可以包含编码L-蛋白的核酸,其中与SEQ ID NO:16所示野生型L-蛋白序列相比,所述L-蛋白包含下列突变组中的一个:Ser1758→Phe(对应于突变株P42的突变);Phe1995→Ser,任选地Ile2094→Val,和任选地Thr2141→Ala(对应于突变株P52的突变,该突变株是对于2094和2141位的寡克隆);Lys1513→Glu,Phe1995→Ser和任选地Arg2175→Lys(对应于突变株P91的突变,该突变株是对于2175位的寡克隆);Lys253→Arg;Lys 1512→Met;Lys2115→Glu;Thr2185→Ala(对应于突变株P52-1的突变);Phe1995→Ser(对应于突变株P52-1.3的突变);或Lys2115→Glu(对应于突变株P52-2.1的突变),和/或可以包含由所述核酸编码的相应蛋白。
本发明所述的LCMV突变体可以包含编码L-蛋白的核酸,其中所述核酸具有如下序列或优选与如下序列互补:所述序列与SEQ ID NO:17、25、33、41、49和57所示序列具有至少约95%、优选至少约96%、优选至少约97%、优选至少约98%、优选至少约99%、优选至少约99.1%、优选至少约99.2%、优选至少约99.3%、优选至少约99.4%、优选至少约99.5%、优选至少约99.6%、优选至少约99.7%、优选至少约99.8%、优选至少约99.9%的序列同一性,或优选与所述序列相同,和/或可以包含由所述核酸编码的相应蛋白。
本发明所述的LCMV突变体可以包含编码核蛋白的核酸,其中所述核蛋白与SEQ IDNO:12、20、28、36、44、52和60中任一个所示核蛋白具有至少约95%、优选至少约96%、优选至少约97%、优选至少约98%、优选至少约99%、优选至少约99.1%、优选至少约99.2%、优选至少约99.3%、优选至少约99.4%、优选至少约99.5%、优选至少约99.6%、优选至少约99.7%的序列同一性,或相同,和/或可以包含由所述核酸编码的相应蛋白。
本发明所述的LCMV突变体可以包含编码核蛋白的核酸,其中所述核酸具有如下序列或优选与如下序列互补:所述序列与SEQ ID NO:11、19、27、35、43、51和59中任一个所示核蛋白具有至少约95%、优选至少约96%、优选至少约97%、优选至少约98%、优选至少约99%、优选至少约99.1%、优选至少约99.2%、优选至少约99.3%、优选至少约99.4%、优选至少约99.5%、优选至少约99.6%、优选至少约99.7%的序列同一性,或相同,和/或可以包含由所述核酸编码的相应蛋白。
本发明所述的LCMV突变体可以包含编码Z-蛋白的核酸,其中所述Z-蛋白与SEQ IDNO:14、22、30、38、46、54和62中任一个所示序列具有至少约95%、优选至少约96%、优选至少约97%、优选至少约98%、优选至少约99%、优选至少约99.1%、优选至少约99.2%、优选至少约99.3%、优选至少约99.4%、优选至少约99.5%、优选至少约99.6%、优选至少约99.7%的序列同一性,或相同,和/或可以包含由所述核酸编码的相应蛋白。
本发明所述的LCMV突变体可以包含编码Z-蛋白的核酸,其中所述核酸包含如下序列:所述序列与SEQ ID NO:13、21、29、37、45、53和61中任一个所示序列具有至少约95%、优选至少约96%、优选至少约97%、优选至少约98%、优选至少约99%、优选至少约99.1%、优选至少约99.2%、优选至少约99.3%、优选至少约99.4%、优选至少约99.5%、优选至少约99.6%、优选至少约99.7%的序列同一性,或相同,和/或可以包含由所述核酸编码的相应蛋白。
本发明所述的LCMV突变体可以包含优选如本文所定义的糖蛋白,优选如本文所定义的L蛋白,优选如本文所定义的Z蛋白和优选如本文所定义的核蛋白。本发明所述的LCMV突变体可以包含核酸,所述核酸编码优选如本文所定义的糖蛋白,优选如本文所定义的L蛋白,优选如本文所定义的Z蛋白和优选如本文所定义的核蛋白。
本发明所述的LCMV突变体可以包含核酸,所述核酸编码SEQ ID NO:18、20、22和24的蛋白,或与这些序列具有至少约95%、优选至少约96%、优选至少约97%、优选至少约98%、优选至少约99%、优选至少约99.1%、优选至少约99.2%、优选至少约99.3%、优选至少约99.4%、优选至少约99.5%、优选至少约99.6%、优选至少约99.7%的序列同一性的蛋白。所述糖蛋白可包含Ile181→Met突变。所述L-蛋白可以包含Ser1758→Phe突变。本发明所述的LCMV突变体可以包含核酸,所述核酸包含SEQ ID NO:17和21所示序列,并且包含与SEQ ID NO:19和23所示序列互补的序列。
本发明所述的LCMV突变体可以包含核酸,所述核酸编码SEQ ID NO:26、28、30和32的蛋白,或与这些序列具有至少约95%、优选至少约96%、优选至少约97%、优选至少约98%、优选至少约99%、优选至少约99.1%、优选至少约99.2%、优选至少约99.3%、优选至少约99.4%、优选至少约99.5%、优选至少约99.6%、优选至少约99.7%的序列同一性的蛋白。所述糖蛋白可以包含Ile181→Met和Arg185→Trp突变。所述L-蛋白可以包含以下突变Phe1995→Ser,任选地Ile2094→Val,和任选地Thr2141→Ala。本发明所述的LCMV突变体可以包含核酸,所述核酸包含SEQ ID NO:25和29所示序列,并且包含与SEQ ID NOs:27和31所示序列互补的序列。
本发明所述的LCMV突变体可以包含核酸,所述核酸编码SEQ ID NO:34、36、38和40的蛋白,或与这些序列具有至少约95%、优选至少约96%、优选至少约97%、优选至少约98%、优选至少约99%、优选至少约99.1%、优选至少约99.2%、优选至少约99.3%、优选至少约99.4%、优选至少约99.5%、优选至少约99.6%、优选至少约99.7%的序列同一性的蛋白。所述糖蛋白可以包含Ile181→Met和Arg185→Trp突变。所述L-蛋白可以包含以下突变Lys1513→Glu,Phe1995→Ser,和任选地Arg2175→Lys。本发明所述的LCMV突变体可以包含核酸,所述核酸包含SEQ ID NO:33和37所示序列,并且包含与SEQ ID NO:35和39所示序列互补的序列。
本发明所述的LCMV突变体可以包含核酸,所述核酸编码SEQ ID NO:50、52、54和56的蛋白,或与这些序列具有至少约95%、优选至少约96%、优选至少约97%、优选至少约98%、优选至少约99%、优选至少约99.1%、优选至少约99.2%、优选至少约99.3%、优选至少约99.4%、优选至少约99.5%、优选至少约99.6%、优选至少约99.7%的序列同一性的蛋白。所述糖蛋白可以包含Ile181→Met和Arg185→Trp突变。所述L-蛋白可以包含以下突变Lys253→Arg;Lys1512→Met;Lys2115→Glu;Thr2185→Ala。本发明所述的LCMV突变体可以包含核酸,所述核酸包含SEQ ID NO:41和45所示序列,并且包含与SEQ ID NO:43和47所示序列互补的序列。
本发明所述的LCMV突变体可以包含核酸,所述核酸编码SEQ ID NO:58、60、62和64的蛋白,或与这些序列具有至少约95%、优选至少约96%、优选至少约97%、优选至少约98%、优选至少约99%、优选至少约99.1%、优选至少约99.2%、优选至少约99.3%、优选至少约99.4%、优选至少约99.5%、优选至少约99.6%、优选至少约99.7%的序列同一性的蛋白。所述糖蛋白可以包含Arg185→Trp突变。所述L-蛋白可以包含Phe1995→Ser突变。本发明所述的LCMV突变体可以包含核酸,所述核酸包含SEQ ID NO:49和53所示序列,并且包含与SEQ ID NO:51和55所示序列互补的序列。
本发明所述的LCMV突变体可以包含核酸,所述核酸编码SEQ ID NO:66、68、70和72的蛋白,或与这些序列具有至少约95%、优选至少约96%、优选至少约97%、优选至少约98%、优选至少约99%、优选至少约99.1%、优选至少约99.2%、优选至少约99.3%、优选至少约99.4%、优选至少约99.5%、优选至少约99.6%、优选至少约99.7%的序列同一性的蛋白。所述糖蛋白可以包含Ile181→Met突变。所述L蛋白可以包含Lys2115→Glu突变。本发明所述的LCMV突变体可以包含核酸,所述核酸包含SEQ ID NO:57和61所示序列,并且包含与SEQ ID NO:59和63所示序列互补的序列。
本文公开的LCMV可以包含核酸,所述核酸编码SEQ ID NO:10、12、14和18的蛋白,或与这些序列具有至少约95%、优选至少约96%、优选至少约97%、优选至少约98%、优选至少约99%、优选至少约99.1%、优选至少约99.2%、优选至少约99.3%、优选至少约99.4%、优选至少约99.5%、优选至少约99.6%、优选至少约99.7%的序列同一性的蛋白。本文公开的LCMV可以包含核酸,所述核酸包含SEQ ID NO:10和14所示序列,并且包含与SEQID NO:12和16所示序列互补的序列。
本发明还大体上涉及用于治疗的本文公开的LCMV,特别是本文公开的LCMV突变体。
特别是当使用本文公开的LCMV突变体时,与野生型淋巴细胞性脉络丛脑膜炎病毒株WE的使用相比,这种使用可以包括所述LCMV突变体在肿瘤(细胞)中更强的繁殖。与LCMV-WE野生型的体内使用相比,这种使用还可以包括诱导更强的天然免疫激活。与LCMV-WE野生型的使用相比,这种使用还可以包括促进更强的体内抗肿瘤作用。与LCMV-WE野生型的使用相比,这种使用还可以包括增加肿瘤特异性CD8+ T细胞的扩增。所述使用还可以包括增强肿瘤特异性CD8+ T细胞的功能。与LCMV-WE野生型相比,所述使用还可以包括更大程度刺激肿瘤特异性T细胞。
本文公开的LCMV(突变体)可以用于治疗和/或预防肿瘤。所述肿瘤可以是本文公开的任何肿瘤。所述肿瘤优选地选自癌、黑色素瘤、母细胞瘤、淋巴瘤和肉瘤。
根据第一方面,本发明涉及用于制备抗肿瘤沙粒病毒的方法,所述抗肿瘤沙粒病毒即对抗肿瘤或排斥肿瘤的沙粒病毒(所谓的消退肿瘤的沙粒病毒),特别是与原始沙粒病毒相比具有改善的抗肿瘤性能、即改善的对抗肿瘤或排斥肿瘤性能的沙粒病毒。
所述方法包括以下步骤:
a)将原代肿瘤细胞在营养培养基、优选液体营养培养基中铺板,或将细胞系H1975、C643或Tramp-C2的细胞在营养培养基、优选液体营养培养基上和/或中铺板;
b)用原始沙粒病毒接种铺板的原代肿瘤细胞或用原始沙粒病毒接种铺板的细胞系H1975、C643或Tramp-C2的细胞;
c)孵育接种的原代肿瘤细胞或孵育接种的细胞系H1975、C643或Tramp-C2的细胞,即在适用于引起至少一部分接种的原代肿瘤细胞或至少一部分接种的细胞系H1975、C643或Tramp-C2的细胞(特别是仅部分的接种的原代肿瘤细胞或仅部分的接种的细胞系H1975、C643或Tramp-C2的细胞,或全部接种的原代肿瘤细胞或全部接种的细胞系H1975、C643或Tramp-C2的细胞)被所述原始沙粒细胞感染的条件下,孵育所述原代肿瘤细胞和所述原始沙粒病毒或孵育细胞系H1975、C643或Tramp-C2的所述细胞和所述原始沙粒病毒,
d)从孵育的原代肿瘤细胞培养物中提取含沙粒病毒的细胞培养物上清液,或从含孵育的细胞系H1975、C643或Tramp-C2的细胞的细胞培养物中提取含沙粒病毒的细胞培养物上清液,
其中步骤顺序a)至d)重复多次,其中当执行步骤顺序a)至d)的第一次重复时,为执行步骤b),用在所述步骤顺序a)至d)的第一次重复之前执行步骤d)时提取的含沙粒病毒的细胞培养上清液或其一部分接种所述原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞,并且其中当执行步骤顺序a)至d)的每次进一步重复时,为执行步骤b),用在执行所述步骤顺序a)至d)的前次重复的步骤d)时提取的含沙粒病毒的细胞培养上清液或其一部分接种所述原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞。
步骤顺序a)至d)的第一次执行也可以被称为在本发明的含义内的“第一次传代”。因此,以原始沙粒病毒作为接种物执行所述第一次传代。然后用在前传代、优选前一次传代的步骤d)中提取的含沙粒病毒的细胞培养上清液或其一部分执行每次进一步传代。从执行第二次传代开始,所述传代可以被称为在本发明的含义内的“重复传代”。
在本发明的上下文中,术语“原始沙粒病毒”可以理解为在步骤顺序a)至d)的第一次重复之前,即所述第一次传代之前用于原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞的接种(步骤b))的沙粒病毒。所述“原始沙粒病毒”可以是指,详述如下,一种野生型沙粒病毒或其突变体。特别地,该术语可以指没有或有抗肿瘤特性的原始沙粒病毒。
本发明上下文中,术语“野生型沙粒病毒”应当被理解为是指具有在自然界中以其遗传正常形式出现的基因组的沙粒病毒。
本发明上下文中,术语“原代肿瘤细胞”应当被理解为是指未传代(unpassaged)或没有传代(non-passaged)的肿瘤细胞,即直接从肿瘤组织分离的肿瘤细胞或在执行步骤a)之前已经传代了最多1000代,特别是最多100代,优选最多10代的直接从肿瘤组织分离的肿瘤细胞,或特征在于具有不同细胞克隆的原代肿瘤细胞。在后者的情况下,异质性可以通过不同的蛋白质表达和不同的DNA序列(遗传指纹)来证明。
在本发明的上下文中,术语“细胞系H1975”应当被理解为是指从人腺癌中分离并保藏在ATCC(美国典型培养物保藏中心)的命名为NCI-H1975
在本发明的上下文中,术语“细胞系C643”应当被理解为是指从人未分化甲状腺癌分离的以命名C643保藏的且访问或保藏编号为CVCL-5969(ExPASy Cellosaurus)的细胞系。
在本发明上下文中,术语“细胞系Tramp-C2”应当被理解为是指从鼠腺癌分离的以命名Tramp-C2保藏的且访问或保藏编号为CVCL-3615(ExPASy Cellosaurus)的细胞系。
在本发明的上下文中,术语“铺板(plating out)”应当被理解为是指将原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞接种到或导入培养基、优选液体培养基上和/或中。换言之,本发明含义中的术语“铺板(plating)”应当被理解为是指原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞在培养基、优选液体培养基上和/或中的培养,特别是初始培养。
术语“淋巴细胞性脉络丛脑膜炎病毒WE株”可以指由Seiler,P.等人报道的LCMV-WE株(Seiler,P.,等人,J.Immunol.162(8),4536-4541(1999))。本文所用术语“淋巴细胞性脉络丛脑膜炎病毒WE株”优选指如下LCMV:所述LCMV包含具有SEQ ID NO:10第59-265位和266-498位序列的糖蛋白,具有SEQ ID NO:12序列的核蛋白;具有SEQ ID NO:14序列的Z-蛋白;和/或具有SEQ ID NO:16序列的L-蛋白。本文所用术语“淋巴细胞性脉络丛脑膜炎病毒WE株”也优选指包含一个或更多,优选两个核酸分子的LCMV,所述核酸分子包含是SEQ IDNO:9、11、13和/或15序列的序列或与所述序列互补的序列。
在本发明上下文中,术语“沙粒病毒突变体”或“沙粒病毒的突变体”应当被理解为是指一种沙粒病毒,其基因组和/或蛋白质组相对于其野生型的基因组和/或蛋白质组具有至少一个突变,特别是至少一个点突变。优选地,术语“沙粒病毒突变体”或“沙粒病毒的突变体”应当被理解为一种具有蛋白、特别是糖蛋白和/或L-蛋白的沙粒病毒,所述蛋白相对于相应野生型沙粒病毒的相应蛋白,特别是糖蛋白和/或L-蛋白具有至少一个突变,优选地,以氨基酸置换形式的突变。
因此,术语“淋巴细胞性脉络丛脑膜炎病毒突变体”应当理解为一种淋巴细胞性脉络丛脑膜炎病毒的突变体,其基因组和/或蛋白质组相对于野生型淋巴细胞性脉络丛脑膜炎病毒的基因组和/或蛋白质组具有至少一个突变,特别是至少一个点突变。优选地,术语“淋巴细胞性脉络丛脑膜炎病毒突变体”应当被理解为是指一种具有蛋白、特别是糖蛋白和/或L-蛋白的沙粒病毒,所述蛋白相对于野生型淋巴细胞性脉络丛脑膜炎病毒的相应蛋白,特别是糖蛋白和/或L-蛋白具有至少一个突变,优选地,以氨基酸置换形式的突变。
在本发明上下文中,术语“糖蛋白”应当被理解为是指由蛋白质(所述蛋白质在某些上下文中也可以被称作蛋白质部分或蛋白质组分)和一个或多个共价键合的碳水化合物基团(糖基团)(特别是单糖和/或寡糖和/或多糖基团)组成的大分子。
除非另有说明,在本发明上下文中,术语“重复传代(repeated passage)”或“重复传代(repeated passaging)”应被理解为单一或重复的过程,在该过程中原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞用由原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞产生的沙粒病毒处理。为此,必须使用用于原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞的培养基,例如含有10%胎牛血清(FKS)和1%青霉素/链霉素/谷氨酰胺(相当于1单位/ml青霉素,100微克(microg)/ml链霉素和2mM L-谷氨酰胺)的DMEM(杜尔贝科改良伊格尔培养基)。未感染的原代肿瘤细胞或未感染的细胞系H1975、C643或Tramp-C2的细胞优选在接种步骤(步骤b)之前0-7天,特别是1-7天铺板。优选地,在接种步骤之前用新鲜培养基替换用于细胞铺板的培养基。在某些情况下,培养基可以在接种步骤(步骤b)之后1分钟、10分钟或100分钟被提取,并用新鲜培养基替换。在孵育24、48、72或96小时的时间段之后,提取含有突变沙粒病毒积累的细胞培养上清液。将该上清液的一部分加入到新的未感染的原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞中。
本文所用术语“核酸”一般可以指DNA或RNA。DNA和RNA——除了别的不同——区别在于它们的核碱基。DNA中腺嘌呤的互补碱基是胸腺嘧啶,而RNA中则是尿嘧啶。为了简化,在整个申请文件中腺嘌呤的对应碱基被表示为“t”,根据上下文,其可以指胸腺嘧啶(在DNA中)或尿嘧啶(在RNA中)。
本文在核酸的上下文中使用的术语“编码(encoding)”或“编码(encode(s))”涉及具有能够被翻译成由该核酸编码的特定氨基酸序列的序列的核酸。所述核酸序列可以包含编码链的序列,也可以包含与所述编码链互补的链的序列。
关于本文公开的序列的“序列同一性百分比(%)”被定义为:在将序列进行比对并引入间隔(如有必要,以获得最大序列同一性百分数)之后,且不将任何保守置换认为是序列同一性的一部分,候选序列中与参考序列中的氨基酸残基或核苷酸成对相同的氨基酸残基或核苷酸的百分数。用于确定氨基酸序列同一性百分比的比对可通过本领域技术范围内的各种方式来实现,例如使用公共可用的计算机软件,例如BLAST、ALIGN或Megalign(DNASTAR)软件。本领域技术人员可以确定用于测量比对的适当参数,包括在被比较序列的全长上实现最大比对所需的任何算法。本文所公开的核苷酸序列也是如此。为了确定序列同一性,(例如RNA中的)尿嘧啶可以被认为与(例如DNA中的)胸腺嘧啶相同。
本发明还基于令人惊奇的发现,即通过被沙粒病毒感染的原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞的传代,可以产生具有抗肿瘤性能的沙粒病毒,特别是与所使用的沙粒病毒相比具有改善的抗肿瘤性能的沙粒病毒。这种沙粒病毒的产生是基于这样的事实,即原始沙粒病毒,通常是野生型沙粒病毒,难以在原代肿瘤细胞或细胞系H1975的细胞中增殖。在细胞系C643和Tramp-C2中观察到同样受限的增殖。在原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞中感染和复制期间,受限的增殖在沙粒病毒中激发增强的选择或适应压力。随机出现的病毒突变体,其能够在原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞中增殖,胜过了原始沙粒病毒,通常是野生型沙粒病毒。通过传代,特别是重复传代(步骤顺序a)至d)的多次重复),优选导致沙粒病毒的富集,所述沙粒病毒对原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞具有抗肿瘤作用,或与原始沙粒病毒相比具有改善的抗肿瘤性能。所述沙粒病毒突变体的抗肿瘤作用是基于它能更好地感染细胞并在细胞内更好地复制的事实。通过这样,与原始沙粒病毒相比,所述沙粒病毒突变体可以更成功地在所用细胞中传播,并且特别是促进增强的免疫激活。由于许多肿瘤细胞不具有任何抗病毒因子,因此表现出有限的病毒抗性,因此根据本发明的方法可不仅对于生产抗肿瘤沙粒病毒,而且对于生产肿瘤特异性沙粒病毒,即对于生产抗肿瘤和肿瘤特异性沙粒病毒特别有优势。
所述原代肿瘤细胞以及细胞系H1975、C643和Tramp-C2的细胞被本发明人确认为这样的细胞,即其令人惊奇地仅允许沙粒病毒衰减的复制并且在传代过程中在沙粒病毒中触发特别高的选择压力或适应性胁迫。
在本发明的一个实施方案中,在执行步骤a)之前,所述原代肿瘤细胞被传代至多1000次,特别是至多100次,优选至多10次。在本文中,术语“传代”应理解为稀释细胞培养物中的细胞,从而将细胞摄取到悬浮液中,并将部分细胞(例如50%、10%或1%)在新的营养培养基中铺板。在步骤a)之前,原代肿瘤细胞被传代得越少,细胞对应于患者肿瘤细胞的特性就越多。特别地,个体原代肿瘤细胞在形态学、RNA表达模式、蛋白质表达和DNA序列上的巨大差异(异质性)决定了体内肿瘤细胞的特性。由此,可以以有利的方式生产沙粒病毒,所述沙粒病毒特别适用于各自的肿瘤患者,特别是其患者群组的治疗。
特别地,在步骤a)之前,所述原代肿瘤细胞可以不经传代。换言之,为了执行步骤a),可以使用未传代的,即没有传代的原代肿瘤细胞。由此,迫使所述原始沙粒病毒或在提取的细胞培养上清液或其一部分中所含的沙粒病毒适应特别能代表患者肿瘤细胞的细胞。通过这样,有可能产生特别适用于各自的肿瘤患者,特别是其患者群组的治疗的沙粒病毒。
细胞系H1975、C643和Tramp-C2的已经经常传代的细胞被发明人确定为是同样合适的细胞,尽管它们已经体外传代多年。
在本发明的另一个实施方案中,步骤c)在1小时至1000小时,特别是3小时至300小时,优选12小时至96小时的时间段内进行。本段中所公开的时间段已经被证明特别有利于用原始沙粒病毒或在提取的细胞培养上清液或其一部分中所含的沙粒病毒对接种的原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的接种的细胞的有效孵育及后续的感染。
在本发明的另一个实施方案中,步骤(b)和/或步骤(c)在4℃至50℃,特别是20℃至42℃,优选34℃至39℃的温度下进行。已经发现本段中所公开的温度范围特别有利于用原始沙粒病毒或在提取的细胞培养上清液或其一部分中所含的沙粒病毒对原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞的有效接种和/或孵育(并继而感染)。
在本发明的另一个实施方案中,步骤a)和/或步骤b)和/或步骤c)和/或步骤d)在营养培养基中执行,所述营养培养基优选选自RPMI-1640(罗斯威尔纪念公园研究所)、DMEM(杜尔贝科改良伊格尔培养基)和IMDM(Iscove′s改良Dulbecco′s培养基)。所述营养培养基还可以含有血清(0.1-20%),如胎牛血清和/或人血清,和/或氨基酸(如谷氨酸和/或谷氨酰胺),和/或抗生素。培养基能够培养原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞。特别地,培养基以特别的优势有利于原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞的生长和/或细胞分裂。本段中提到的所述培养基特别适用于原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞的培养。
在本发明的另一个实施方案中,步骤a)和/或步骤b)和/或步骤c)在0%-20%,特别是0.1%-20%,优选2%-10%,更优选4%-6%的二氧化碳气氛(CO
优选地,步骤a)和/或步骤b)和/或步骤c)在培养箱中执行,通过该设备可以创造用于原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞生长和/或细胞分裂的受控外部条件。
在本发明的另一个实施方案中,步骤a)至d)的顺序重复3次至1000次,特别是10次至100次,优选20次至50次。步骤顺序a)至d)的多次重复,特别是本段中公开的重复次数,已经被证明对在抗肿瘤特性方面有益的突变、特别是点突变的发展,以及继而对抗肿瘤沙粒病毒的产生,是特别有益的。
在本发明的另一个实施方案中,在执行步骤b)之前,用新鲜或新的营养培养基替换所述营养培养基。通过该步骤,可以有利地使感染条件标准化。
在本发明的另一个实施方案中,在步骤b)之后,在0.1分钟至600分钟,特别是1分钟至30分钟,优选5分钟至15分钟的时间段内,用新鲜或新的培养基替换所述营养培养基。由于感染时间受限,该步骤有利地增加了感染的选择压力。
在本发明的另一个实施方案中,进行多次营养培养基的更换。例如,在步骤b)之前,所述营养培养基可以用新鲜的或新的营养培养基替换,并且在执行步骤b)之后,在0.1分钟至600分钟,特别是1分钟至30分钟,优选5分钟至15分钟的时间段内,后者可以用新鲜的或新的营养培养基替换。
在本发明的另一个实施方案中,在执行步骤d)之前,特别是在执行步骤c)之前,特别是在执行步骤b)之前,特别是在执行步骤a)之前,用至少一种化疗剂处理原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞和/或原始沙粒病毒和/或在提取的细胞培养上清液或其一部分中所含的沙粒病毒。由此,可以模拟已经进行过化学治疗的肿瘤细胞。这有利地允许生产沙粒病毒,所述沙粒病毒特别适合于治疗已经用化疗治疗过和/或认为已经经历了所有治疗选择的肿瘤患者。
在本发明的另一个实施方案中,在执行步骤b)之前,用至少一种化疗剂处理原始沙粒病毒和/或在提取的细胞培养上清液或其一部分中包含的沙粒病毒。由此,可以有利地提高沙粒病毒中的天然突变率,并因此加速其对原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞的适应。
所述至少一种化疗剂可特别地选自烷基化剂、拓扑异构酶抑制剂、有丝分裂抑制剂、抗代谢剂、抗生素、激酶抑制剂、沙利度胺衍生物、细胞凋亡诱导剂、生物治疗剂(如生物类细胞抑制剂)、含同位素的化合物、激素、激素拮抗剂、组蛋白去乙酰酶抑制剂和其它细胞抑制剂。
所述烷基化剂可选自噁唑磷、N-丢失衍生物、烷基磺酸盐、肼、含铂物质、蒽环类和至少两种上述烷基化剂的混合物。
所述噁唑磷可以例如选自环磷酰胺、异环磷酰胺及其混合物。
所述N-丢失衍生物可以选自苯丁酸氮芥、苯丙氨酸氮芥及其混合物。
所述烷基磺酸盐可以是例如husulfan。
所述肼可以例如选自替莫唑胺、达卡巴嗪、原卡巴嗪和至少两种上述肼的混合物。
所述含铂物质可以例如选自顺铂、卡铂、奥沙利铂和至少两种所述含铂物质的混合物。
所述蒽环类可以例如选自多柔比星、柔红霉素、依达柔比星、表阿霉素和至少两种所述蒽环类的混合物。
上述拓扑异构酶抑制剂可选自拓扑异构酶I抑制剂、拓扑异构酶II抑制剂(依托泊苷)及其混合物。
例如,所述拓扑异构酶I抑制剂可以选自伊立替康、拓扑替康及其混合物。
拓扑异构酶II抑制剂可以是例如依托泊苷。
上述有丝分裂抑制剂或抗代谢剂可选自长春花生物碱类、紫杉烷类、叶酸拮抗剂、嘧啶拮抗剂、嘌呤拮抗剂、核糖核苷酸还原酶抑制剂和至少两种上述有丝分裂抑制剂或抗代谢物的混合物。
例如,长春花生物碱类可以选自长春新碱、长春碱及其混合物。
紫杉烷类可选自多西他赛、紫杉醇及其混合物。
例如,所述叶酸拮抗剂可选自甲氨蝶呤、培美曲塞及其混合物。
所述嘧啶拮抗剂可以例如选自阿糖胞苷、5-氟尿嘧啶、吉西他滨、卡培他滨和至少两种所述嘧啶拮抗剂的混合物。
所述嘌呤拮抗剂可以例如选自5-氮胞苷、硫唑嘌呤、6-巯基嘌呤、氟达拉滨和至少两种所述嘌呤拮抗剂的混合物。
例如,所述核糖核苷酸还原酶抑制剂可以是羟基脲。
上述抗生素可选自博来霉素、放线菌素D、丝裂霉素和至少两种上述抗生素的混合物。
上述激酶抑制剂可以选自阿法替尼、阿利克替尼、阿西替尼、克里唑替尼、科比美替尼、达沙替尼、达拉非尼、埃罗替尼、吉非替尼、伊马替尼、伊沙佐米、乐伐替尼、尼洛替尼、奥希替尼、帕博西尼、帕唑帕尼、普纳替尼、瑞戈非尼、舒尼替尼、维莫非尼、曲美替尼、伊维莫司和至少两种所述激酶抑制剂的混合物。
上述沙利度胺衍生物可选自来那度胺、泊马度胺及其混合物。
上述细胞凋亡诱导剂可选自甲氧嘧啶(methoxal)、维奈托克及其混合物。
上述生物治疗剂可选自利妥昔单抗、曲妥珠单抗、西妥昔单抗、帕尼妥珠单抗、伊匹莫单抗、喷布瑞珠单抗、纳武单抗、阿特珠单抗、阿维单抗、纳武单抗、奥拉木单抗、拉鲁珠单抗(ramucirumab)和至少两种上述生物治疗剂的混合物。
上述激素和/或激素拮抗剂可选自布舍瑞林、戈舍瑞林、亮丙瑞林、曲普瑞林、雌莫司汀、他莫昔芬、芳香化酶抑制剂(如阿那曲唑)、雄激素拮抗剂(如恩扎鲁胺、氟他胺、比卡鲁胺)、孕酮(如醋酸甲地孕酮和醋酸甲羟孕酮)、糖皮质激素以及至少两种上述激素和/或激素拮抗剂的混合物。
上述的其它细胞抑制剂可以选自贝沙罗汀、阿法替尼、克唑替尼、埃罗替尼、吉非替尼、拉帕替尼、达沙替尼、伊马替尼、尼洛替尼、普纳替尼、瑞戈非尼、索尼德吉、羟基脲、曲美替尼、维甲酸(tretininoin)、异维甲酸(isotretinoin)、阿利维甲酸(alitretinoin)、MAOP(5-氨基-4-氧代戊酸甲酯)和至少两种上述其它细胞抑制剂的混合物。
此外,在执行步骤d)之前,特别是在执行步骤c)之前,特别是在执行步骤b)之前,特别是在执行步骤a)之前,所述原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞和/或原始沙粒病毒和/或在提取的细胞培养上清液或其一部分中包含的沙粒病毒可以用辐射处理,所述辐射特别选自紫外(UV)射线(特别是UVA射线和/或UVB射线射线)、α射线、β射线、γ射线和X射线。由此,可以有利地模拟已经受到治疗辐射的肿瘤细胞。这有利地允许生产沙粒病毒,所述沙粒病毒可特别用于已接受辐射治疗的肿瘤患者。
此外,在执行步骤b)之前,所述原始沙粒病毒和/或在提取的细胞培养上清液或其一部分中包含的沙粒病毒用辐射处理,所述辐射特别选自紫外(UV)射线(特别是UVA射线和/或UVB射线)、α射线、β射线、γ射线和X射线。由此,可有利地提高沙粒病毒中的天然突变率及其对原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞的适应性。
在本发明的另一个实施方案中,使用对至少一种化疗剂耐药的原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞。例如,可以使用对紫杉醇和/或曲美替尼耐药的原代肿瘤细胞。因此,可以有利地模拟在肿瘤治疗期间对至少一种化疗剂耐药的患者的肿瘤细胞。在本段中描述的本发明的实施方案因此代表了生产强效抗肿瘤沙粒病毒的进一步可能性。
在本发明的另一个实施方案中,在执行步骤d)之前,特别是在执行步骤c)之前,特别是在执行步骤b)之前,特别是在执行步骤a)之前,所述原代肿瘤细胞或细胞系H1975、C643或Tramp-C2的细胞和/或原始沙粒病毒和/或在提取的细胞培养上清液或其一部分中包含的沙粒病毒用至少一种抗病毒化合物,特别是α-干扰素和/或γ-干扰素处理。由此,可以有利地迫使原始沙粒病毒或在提取的细胞培养上清液或其一部分中包含的沙粒病毒适应抗病毒环境,由此可以产生同时表现出抗性的抗肿瘤沙粒病毒。从治疗的角度看,这种沙粒病毒是特别有效的,因为它也可用于对抗可能表现出病毒抗性的肿瘤组织。
此外,所述方法还可以包括步骤e)通过克隆和/或PCR(聚合酶链反应)和/或测序从提取的细胞培养上清液或其一部分中分离和/或鉴定抗肿瘤沙粒病毒,特别是相对于原始沙粒病毒具有改善的抗肿瘤性能的沙粒病毒。
优选使用的原代肿瘤细胞是原代恶性肿瘤细胞,特别是原代癌细胞、原代黑色素瘤细胞、原代母细胞瘤细胞、原代淋巴瘤细胞或原代肉瘤细胞。
在本发明的另一个实施方案中,原代肿瘤细胞是原代脉络膜黑色素瘤细胞、原代肛门癌细胞、原代血管肉瘤细胞、原代星形细胞瘤细胞、原代基底细胞癌细胞、原代宫颈癌细胞、原代软骨肉瘤细胞、原代绒毛膜癌细胞、原代真皮鳞状细胞癌细胞、原代小肠癌细胞、原代性子宫内膜癌细胞、原代尤文肉瘤细胞、原代纤维肉瘤细胞、原代胆囊癌细胞、原代胆管癌细胞、原代胶质母细胞瘤细胞、原代膀胱癌细胞、原代输尿管癌细胞、原代尿道癌细胞、原代肝细胞癌细胞、原代睾丸肿瘤细胞、原代下咽癌细胞、原代垂体癌细胞、原代卡波西肉瘤细胞、原代小细胞支气管癌细胞、原代结肠癌细胞、原代结直肠癌细胞、原代喉癌细胞、原代平滑肌肉瘤细胞、原代脂肪肉瘤细胞、原代胃癌细胞、原代恶性纤维组织细胞瘤细胞、原代乳腺癌细胞、原代成髓细胞瘤细胞、原代黑色素瘤细胞、原代口腔底癌细胞、原代鼻窦癌细胞、原代鼻咽癌细胞、原代肾上腺皮质癌细胞、原代甲状旁腺癌细胞、原代神经源性肉瘤细胞、原代非小细胞支气管癌细胞、原代肾癌细胞、原代口咽癌细胞、原代骨肉瘤细胞、原代卵巢癌细胞、原代胰腺肿瘤细胞、原代阴茎癌细胞、原代嗜铬细胞瘤细胞、原代胸膜间皮瘤细胞、原代前列腺癌细胞、原代直肠癌细胞、原代视网膜母细胞瘤细胞、原代横纹肌肉瘤细胞、原代甲状腺癌细胞、原代唾液腺癌细胞、原代食管癌细胞、原代扁桃体癌细胞、原代阴道癌细胞、原代外阴癌细胞、原代肾母细胞瘤细胞、原代神经内分泌肿瘤细胞或原代舌癌细胞。
特别优选的是原代黑色素瘤细胞、原代肺癌细胞、原代胰腺癌细胞、原代结肠癌细胞、原代胃癌细胞、原代咽癌细胞、原代喉癌细胞、原代肾细胞癌细胞是特别优选的原代肿瘤细胞,原代卵巢癌细胞、原代子宫内膜癌细胞、原代甲状腺癌细胞、原代前列腺癌细胞、原代肝癌细胞或原代肉瘤细胞(如原代神经源性肉瘤细胞、原代骨肉瘤细胞或原代横纹肌肉瘤细胞)。
在本发明的另一个实施方案中,野生型沙粒病毒,即所谓的野生型沙粒病毒被用作所述原始沙粒病毒。
在本发明的另一个实施方案中,旧大陆沙粒病毒被用作所述原始沙粒病毒。优选地,所述旧大陆沙粒病毒选自卡塔琳娜病毒(Catarina Virus)、丹芬农病毒(DanfenongVirus)、伊派病毒(Ippy Virus,IP-PYV)、克多克病毒(Kodoko Virus)、拉沙病毒(LassaVirus,LASV)、淋巴细胞性脉络丛脑膜炎病毒(Lymphocytic choriomeningitis virus,LCMV)、莫若戈若病毒(Morogoro Virus)、莫巴拉病毒(Mobala Virus,MOBV)、盖若病毒(Gairo Virus)和莫佩亚病毒(Mopeia Virus,MOPV)、平哈病毒(Pinhal Virus)、斯金纳坦克病毒(Skinner Tank Virus)。
淋巴细胞性脉络丛脑膜炎病毒,特别是野生型淋巴细胞性脉络丛脑膜炎病毒优选作为原始沙粒病毒。例如,淋巴细胞性脉络丛脑膜炎病毒的毒株,特别是选自WE、阿姆斯特朗(Armstrong)、克隆13(Clone13)和道塞而(Docile)的毒株可用作原始沙粒病毒。
特别优选的是野生型淋巴细胞性脉络丛脑膜炎病毒,即一种包含L-蛋白和/或核酸(特别是核糖核酸,优选L-核糖核酸)的野生型淋巴细胞性脉络丛脑膜炎病毒,所述L-蛋白包含根据SEQ ID NO:7的氨基酸序列或由所述氨基酸序列组成,所述核酸包含与根据SEQID NO:8的核酸序列互补的核酸序列(特别是核糖核酸序列,优选L-核糖核酸序列)或由所述核酸序列组成。
此外,新大陆沙粒病毒可用作原始沙粒病毒。所述新大陆沙粒病毒优选地选自奥尔帕瓦约病毒(Allpahuayo Virus,ALLV)、阿马帕里病毒(Amapari Virus,AMAV)、熊峡谷病毒(Bear Canyon Virus,BCNV)、恰巴雷病毒(Chapare Virus)、卡皮生病毒(Cupixi Virus,CPXV)、弗雷克索病毒(Flexal Virus,FLEV)、瓜纳里托病毒(Guanarito Virus,GTOV)、胡宁病毒(Junin Virus,JUNV)、Candid#1(Candid 1号)、拉蒂诺病毒(Latino virus,LATV)、马楚普病毒(Machupo virus,MACV)、奥利华恩病毒(Oliveros virus,OLVV)、巴拉那病毒(Parana virus,PARV)、皮钦德病毒(Pichinide virus,PICV)、皮雷特尔病毒(Piritalvirus,PIRV)、萨比埃病毒(Sabia virus,SABV)、塔卡里博病毒(Taribe virus,TCRV)、太米阿米病毒(Tamiami virus,TAMV)和怀特沃特阿罗约病毒(Whitewater arroyo virus,WWAV)。
此外,没有抗肿瘤特性的沙粒病毒可以用作所述原始沙粒病毒。
或者,可以使用具有抗肿瘤特性的原始沙粒病毒。
根据第二方面,本发明涉及淋巴细胞性脉络丛脑膜炎病毒突变体,即淋巴细胞性脉络丛脑膜炎病毒的突变体。
所述淋巴细胞性脉络丛脑膜炎病毒突变体包含蛋白或肽,特别是糖蛋白。所述蛋白或肽包含突变,特别是点突变。该突变,特别是点突变,优选不同于序列AJ297484、AJ233196和参考序列LCMV(毒株WE-Essen)。
优选地,所述淋巴细胞性脉络丛脑膜炎病毒突变体包含具有至少一个突变的糖蛋白,特别是糖蛋白的蛋白组分或蛋白部分,其中所述至少一个突变是所述糖蛋白的181位异亮氨酸被另一个氨基酸、优选蛋氨酸的氨基酸置换,和/或所述糖蛋白的185位精氨酸被另一个氨基酸、优选色氨酸的氨基酸置换。
可选地或组合地,所述淋巴细胞性脉络丛脑膜炎病毒突变体优选地包含具有至少一个突变的L-蛋白,其中所述至少一个突变是L-蛋白的1513位赖氨酸被另一个氨基酸、优选谷氨酸的氨基酸置换,和/或L-蛋白的1995位苯丙氨酸被另一个氨基酸、优选丝氨酸的氨基酸置换,和/或L-蛋白的2094位异亮氨酸被另一个氨基酸、优选缬氨酸的氨基酸置换,和/或L-蛋白的2141位苏氨酸被另一个氨基酸、优选丙氨酸的氨基酸置换,和/或L-蛋白的2175位精氨酸被另一个氨基酸、优选赖氨酸的氨基酸置换。
可选地或组合地,所述淋巴细胞性脉络丛脑膜炎病毒突变体优选地包含蛋白或肽,特别是糖蛋白(特别是糖蛋白的蛋白组分或蛋白部分),或L-蛋白,所述蛋白或肽包含根据SEQ ID NO:1、SEQ ID NO:3、SEQ ID NO:5、SEQ ID NO:18、SEQ ID NO:26、SEQ ID NO:34、SEQ ID NO:42、SEQ ID NO:50、SEQ ID NO:58、SEQ ID NO:24、SEQ ID NO:32、SEQ ID NO:40、SEQ ID NO:48、SEQ ID NO:56和SEQ ID NO:64的氨基酸序列或由所述氨基酸序列组成。根据SEQ ID NO:1、SEQ ID NO:3、SEQ ID NO:18、SEQ ID NO:26、SEQ ID NO:34、SEQ ID NO:42、SEQ ID NO:50和SEQ ID NO:58的氨基酸序列优选地为淋巴细胞性脉络丛脑膜炎病毒突变体的糖蛋白的氨基酸序列。SEQ ID NO:5、SEQ ID NO:24、SEQ ID NO:32、SEQ ID NO:40、SEQ ID NO:48、SEQ ID NO:56和SEQ ID NO:64的氨基酸序列优选为淋巴细胞性脉络丛脑膜炎病毒突变体的L-蛋白的氨基酸序列。
可选地或组合地,所述淋巴细胞性脉络丛脑膜炎病毒突变体优选地包含编码蛋白或肽,特别是糖蛋白或L-蛋白的核酸,特别是核糖核酸,所述蛋白或肽包含根据SEQ ID NO:1、SEQ ID NO:3、SEQ ID NO:5、SEQ ID NO:18、SEQ ID NO:26、SEQ ID NO:34、SEQ ID NO:42、SEQ ID NO:50、SEQ ID NO:58、SEQ ID NO:24、SEQ ID NO:32、SEQ ID NO:40、SEQ IDNO:48、SEQ ID NO:56或SEQ ID NO:64的氨基酸序列或由所述氨基酸序列组成。
可选地或组合地,所述淋巴细胞性脉络丛脑膜炎病毒突变体优选地包含核酸,特别是核糖核酸,其包含核酸序列,特别是核糖核酸序列,或者由核酸序列,特别是核糖核酸序列组成,所述核酸序列与根据SEQ ID NO:2、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:17、SEQ ID NO:25、SEQ ID NO:33、SEQ ID NO:41、SEQ ID NO:49、SEQ ID NO:57、SEQ ID NO:23、SEQ ID NO:31、SEQ ID NO:39、SEQ ID NO:47、SEQ ID NO:55或SEQ ID NO:56的核酸序列互补。
令人惊奇地发现所述淋巴细胞性脉络丛脑膜炎病毒的相应一个或多个突变体——如前面段落中所描述的——特别是相较野生型淋巴细胞性脉络丛脑膜炎病毒,在原代肿瘤细胞或细胞系H1975的细胞中具有改善的复制能力,以及抗肿瘤性能或改善的抗肿瘤性能。
此外,优选编码所述糖蛋白181位异亮氨酸的密码子被另一个密码子替换,优选被编码蛋氨酸的密码子替换。
此外,优选编码所述糖蛋白185位精氨酸的密码子被另一个密码子替换,优选被编码色氨酸的密码子替换。
此外,优选编码所述糖蛋白155位组氨酸的密码子被另一个密码子替换,优选被编码酪氨酸的密码子替换。
此外,优选编码所述糖蛋白358位精氨酸的密码子被另一个密码子替换,优选被编码赖氨酸的密码子替换。
此外,还优选所述淋巴细胞性脉络丛脑膜炎病毒突变体包含包括突变的核酸,特别是核糖核酸,优选L-核糖核酸,其中所述突变是所述核酸(特别是核糖核酸,优选L-核糖核酸)4537位腺嘌呤被鸟嘌呤的核苷酸置换。
此外,优选所述淋巴细胞性脉络丛脑膜炎病毒突变体包含编码包含突变的L-蛋白的核酸,特别是核糖核酸,优选L-核糖核酸,其中所述突变是L-蛋白的1513位赖氨酸被另一个氨基酸、优选谷氨酸的氨基酸置换。
此外,优选所述淋巴细胞性脉络丛脑膜炎病毒突变体包含编码包含突变的L-蛋白的核酸,特别是核糖核酸,优选L-核糖核酸,其中所述突变是L-蛋白的1995位苯丙氨酸被另一个氨基酸、优选丝氨酸的氨基酸置换。
此外,还优选所述淋巴细胞性脉络丛脑膜炎病毒突变体包含包括突变的核酸,特别是核糖核酸,优选L-核糖核酸,其中所述突变是所述核酸(特别是核糖核酸,优选L-核糖核酸)的5984位胸腺嘧啶优选地被核苷酸胞嘧啶的核苷酸置换。
此外,还优选所述淋巴细胞性脉络丛脑膜炎病毒突变体包含编码包含突变的L-蛋白的核酸,特别是核糖核酸,优选L-核糖核酸,其中所述突变是L-蛋白的2094位异亮氨酸被另一个氨基酸、优选缬氨酸的氨基酸置换。
此外,还优选所述淋巴细胞性脉络丛脑膜炎病毒突变体包含包括突变的核酸,特别是核糖核酸,优选L-核糖核酸,其中所述突变是所述核酸(特别是核糖核酸,优选L-核糖核酸)的核苷酸6280位腺嘌呤被另一个核苷酸、优选鸟嘌呤的核苷酸置换。
此外,优选所述淋巴细胞性脉络丛脑膜炎病毒突变体包含编码包含突变的L-蛋白的核酸,特别是核糖核酸,优选L-核糖核酸,其中所述突变是L-蛋白的2141位苏氨酸被另一个氨基酸、优选丙氨酸的氨基酸置换。
此外,还优选所述淋巴细胞性脉络丛脑膜炎病毒突变体包含包括突变的核酸,特别是核糖核酸,优选L-核糖核酸,其中所述突变是所述核酸(特别是核糖核酸,优选L-核糖核酸)的6421位腺嘌呤优选地被另一个核苷酸、优选鸟嘌呤的核苷酸置换。
此外,还优选所述淋巴细胞性脉络丛脑膜炎病毒突变体包含编码包含突变的L-蛋白的核酸,特别是核糖核酸,优选L-核糖核酸,其中所述突变是L-蛋白的2175位精氨酸优选被赖氨酸的氨基酸置换。
此外,还优选所述淋巴细胞性脉络丛脑膜炎病毒突变体包含包括突变的核酸,特别是核糖核酸,优选L-核糖核酸,其中所述突变是所述核酸(特别是核糖核酸,优选L-核糖核酸)的6524位鸟嘌呤被核苷酸腺嘌呤的核苷酸置换。
在本发明的另一个实施方案中,所述淋巴细胞性脉络丛脑膜炎病毒突变体是用于在医药中应用或使用的淋巴细胞性脉络丛脑膜炎病毒突变体,包括本文公开的任何淋巴细胞性脉络丛脑膜炎病毒突变体。
优选地,所述淋巴细胞性脉络丛脑膜炎病毒突变体是用于在治疗和/或预防肿瘤中应用或使用的淋巴细胞性脉络丛脑膜炎病毒突变体。
所述肿瘤优选地选自癌、黑色素瘤、母细胞瘤、淋巴瘤和肉瘤。
在本发明上下文中,术语“癌”应当理解为是指上皮来源的恶性肿瘤。
在本发明上下文中,术语“肉瘤”应当理解为是指中胚层来源的恶性肿瘤。
在本发明上下文中,术语“黑色素瘤”应当理解为是指黑素细胞来源的恶性肿瘤。
在本发明上下文中,术语“淋巴瘤”应当理解为是指淋巴细胞来源的恶性肿瘤。
在本发明上下文中,术语“母细胞瘤”应当理解为是指胚胎来源的恶性肿瘤。
所述癌优选地选自肛门癌、支气管癌、肺癌、子宫内膜癌、胆囊癌、膀胱癌、肝细胞癌、睾丸癌、结肠癌、结直肠癌、直肠癌、喉癌、食道癌、胃癌、乳腺癌、肾癌、卵巢癌、胰腺癌、咽癌、口咽癌、前列腺癌、甲状腺癌和宫颈癌。
所述肉瘤可选自血管肉瘤、软骨肉瘤、尤文肉瘤、纤维肉瘤、卡波西肉瘤、脂肪肉瘤、平滑肌肉瘤、恶性纤维组织细胞瘤、神经源性肉瘤、骨肉瘤和横纹肌肉瘤。
此外,所述淋巴细胞性脉络丛脑膜炎病毒突变体可以制备成或用于局部,特别是肌肉内、腹膜内或皮下给药。
或者,所述淋巴细胞性脉络丛脑膜炎病毒突变体可以制备成或用于全身,特别是静脉给药。
对于所述淋巴细胞性脉络丛脑膜炎病毒突变体的进一步特征和益处,完全参考前面和下面的描述。
根据第三方面,本发明涉及一种淋巴细胞性脉络丛脑膜炎病毒突变体,其包含蛋白或肽、特别是糖蛋白或L-蛋白,或由所述蛋白或肽组成,所述蛋白或肽包含根据SEQ IDNO:1、SEQ ID NO:3、SEQ ID NO:5、SEQ ID NO:18、SEQ ID NO:26、SEQ ID NO:34、SEQ IDNO:42、SEQ ID NO:50、SEQ ID NO:58、SEQ ID NO:66、SEQ ID NO:24、SEQ ID NO:32、SEQ IDNO:40、SEQ ID NO:48、SEQ ID NO:56或SEQ ID NO:64的氨基酸序列或由所述氨基酸序列组成。
可选地或组合地,所述淋巴细胞性脉络丛脑膜炎病毒突变体包含核酸、特别是核糖核酸,其中所述核酸、特别是核糖核酸包含核酸序列、特别是核糖核酸序列,或者由核酸序列、特别是核糖核酸序列组成,所述核酸序列是根据SEQ ID NO:2、SEQ ID NO:4、SEQ IDNO:6、SEQ ID NO:17、SEQ ID NO:25、SEQ ID NO:33、SEQ ID NO:41、SEQ ID NO:49、SEQ IDNO:57、SEQ ID NO:65、SEQ ID NO:23、SEQ ID NO:31、SEQ ID NO:39、SEQ ID NO:47、SEQ IDNO:55或SEQ ID NO:63的核酸序列或与所述核酸序列互补。
优选地,所述淋巴细胞性脉络丛脑膜炎病毒突变体是用于在医药中应用或使用的淋巴细胞性脉络丛脑膜炎病毒突变体。
所述淋巴细胞性脉络丛脑膜炎病毒突变体特别优选地是用于在治疗和/或预防肿瘤中应用或使用的淋巴细胞性脉络丛脑膜炎病毒突变体。
所述肿瘤优选地选自癌、黑色素瘤、母细胞瘤、淋巴瘤和肉瘤。
在本发明上下文中,术语“癌”应当理解为是指上皮来源的恶性肿瘤。
在本发明上下文中,术语“肉瘤”应当理解为是指中胚层来源的恶性肿瘤。
在本发明上下文中,术语“黑色素瘤”应当理解为是指黑素细胞来源的恶性肿瘤。
在本发明上下文中,术语“淋巴瘤”应当理解为是指淋巴细胞来源的恶性肿瘤。
在本发明上下文中,术语“母细胞瘤”应当理解为是指胚胎来源的恶性肿瘤。
所述癌优选地选自肛门癌、支气管癌、肺癌、子宫内膜癌、胆囊癌、膀胱癌、肝细胞癌、睾丸癌、结肠癌、结直肠癌、直肠癌、喉癌、食道癌、胃癌、乳腺癌、肾癌、卵巢癌、胰腺癌、咽癌、口咽癌、前列腺癌、甲状腺癌和宫颈癌。
所述肉瘤可选自血管肉瘤、软骨肉瘤、尤文肉瘤、纤维肉瘤、卡波西肉瘤、脂肪肉瘤、平滑肌肉瘤、恶性纤维组织细胞瘤、神经源性肉瘤、骨肉瘤和横纹肌肉瘤。
此外,所述淋巴细胞性脉络丛脑膜炎病毒突变体可以制备成或用于局部,特别是肌肉内、腹膜内或皮下给药。
或者,所述淋巴细胞性脉络丛脑膜炎病毒突变体可以制备成或用于全身,特别是静脉给药。
对于所述淋巴细胞性脉络丛脑膜炎病毒突变体的进一步特征和益处,为了避免重复,也完全参考前面的描述,特别是在本发明第二方面的上下文中所作的说明。其中所述的特征和优点,特别是关于所述淋巴细胞性脉络丛脑膜炎病毒突变体、所述蛋白或肽(特别是糖蛋白)和所述核酸(特别是核糖核酸)的特征和优点,(加以必要的修正)也适用于根据本发明第三方面的所述淋巴细胞性脉络丛脑膜炎病毒突变体。
根据第四方面,本发明涉及包含根据本发明第二或第三方面的淋巴细胞性脉络丛脑膜炎病毒突变体的药物或药剂。
所述药物或药剂还可包含检查点阻断剂,如PD-1(编程性细胞死亡蛋白1),和/或细胞凋亡调节剂,特别是细胞凋亡抑制剂例如SMAC-模拟物(mimeticum)(LCL-161)。
所述药物或药剂优选地还包含药学上可接受的载体。所述载体可选自水、水性盐水溶液、水性缓冲溶液、细胞培养基和至少两种前述载体的组合。
对于所述药物或药剂的进一步特征和益处,为了避免重复,完全参考前面的描述,特别是在本发明的第二和第三方面的上下文中所作的说明。其中所述的特征和优点,特别是关于所述淋巴细胞性脉络丛脑膜炎病毒突变体的特征和优点,(加以必要的修正)也适用于本发明第四方面所述的药物或药剂。
根据第五方面,本发明涉及一种蛋白或肽,其优选为分离的蛋白或肽,特别是糖蛋白或L-蛋白,所述分离的蛋白或肽包含根据SEQ ID NO:1、SEQ ID NO:3、SEQ ID NO:5、SEQID NO:7、SEQ ID NO:10、SEQ ID NO:18、SEQ ID NO:26、SEQ ID NO:34、SEQ ID NO:42、SEQID NO:50、SEQ ID NO:58、SEQ ID NO:24、SEQ ID NO:32、SEQ ID NO:40、SEQ ID NO:48、SEQID NO:56或SEQ ID NO:64的氨基酸序列或由所述氨基酸序列组成。本发明还涉及分离的蛋白或肽,其与SEQ ID NO:1、SEQ ID NO:3、SEQ ID NO:5、SEQ ID NO:7、SEQ ID NO:10、SEQID NO:18、SEQ ID NO:26、SEQ ID NO:34、SEQ ID NO:42、SEQ ID NO:50、SEQ ID NO:58、SEQID NO:24、SEQ ID NO:32、SEQ ID NO:40、SEQ ID NO:48、SEQ ID NO:56或SEQ ID NO:64具有至少约95%、优选至少约96%、优选至少约97%、优选至少约98%、优选至少约99%、优选至少约99.1%、优选至少约99.2%、优选至少约99.3%、优选至少约99.4%、优选至少约99.5%、优选至少约99.6%、优选至少约99.7%的序列同一性。
根据SEQ ID NO:1和SEQ ID NO:3的氨基酸序列优选是淋巴细胞性脉络丛脑膜炎病毒突变体的糖蛋白、特别是糖蛋白的蛋白组分或蛋白部分的氨基酸序列。根据SEQ IDNO:5的氨基酸序列优选为淋巴细胞性脉络丛脑膜炎病毒突变体的L-蛋白的氨基酸序列。SEQ ID NO:7的氨基酸序列优选为野生型淋巴细胞性脉络丛脑膜炎病毒的L-蛋白的氨基酸序列。
本发明还涉及蛋白或肽,其优选为分离的蛋白或肽,特别是核蛋白或Z-蛋白,所述分离的蛋白或肽包含根据SEQ ID NO:12、SEQ ID NO:20、SEQ ID NO:28、SEQ ID NO:36、SEQID NO:44、SEQ ID NO:52、SEQ ID NO:60、SEQ ID NO:14、SEQ ID NO:22、SEQ ID NO:30、SEQID NO:38、SEQ ID NO:46、SEQ ID NO:54或SEQ ID NO:62的氨基酸序列或由所述氨基酸序列组成。本发明还涉及分离的蛋白或肽,其与SEQ ID NO:12、SEQ ID NO:20、SEQ ID NO:28、SEQ ID NO:36、SEQ ID NO:44、SEQ ID NO:52、SEQ ID NO:60、SEQ ID NO:14、SEQ ID NO:22、SEQ ID NO:30、SEQ ID NO:38、SEQ ID NO:46、SEQ ID NO:54或SEQ ID NO:62具有至少约95%、优选至少约96%、优选至少约97%、优选至少约98%、优选至少约99%、优选至少约99.1%、优选至少约99.2%、优选至少约99.3%、优选至少约99.4%、优选至少约99.5%、优选至少约99.6%、优选至少约99.7%的序列同一性。
关于所述蛋白或肽的进一步特征和优点,为了避免重复,也完全参考前面的描述,特别是在本发明的第二和第三方面所作的说明。其中所述的优点和特征,特别是关于所述蛋白或肽、特别是糖蛋白的优点和特征,(加以必要的修正)也适用于根据本发明第五方面的所述分离的蛋白或肽。
根据第六方面,本发明涉及核酸,其优选为分离的核酸,特别是核糖核酸,所述分离的核酸包含根据SEQ ID NO:2、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:17、SEQ ID NO:25、SEQ ID NO:33、SEQ ID NO:41、SEQ ID NO:49、SEQ ID NO:57、SEQ ID NO:23、SEQ ID NO:31、SEQ ID NO:39、SEQ ID NO:47、SEQ ID NO:55或SEQ IDNO:63的核酸序列或与SEQ ID NO:2、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:17、SEQ ID NO:25、SEQ ID NO:33、SEQ ID NO:41、SEQ ID NO:49、SEQ ID NO:57、SEQ ID NO:23、SEQ ID NO:31、SEQ ID NO:39、SEQ ID NO:47、SEQ ID NO:55或SEQ IDNO:63互补的核酸序列、特别是核糖核酸序列,或由所述核酸序列组成。本发明还涉及分离的蛋白或肽,其与SEQ ID NO:2、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:17、SEQ ID NO:25、SEQ ID NO:33、SEQ ID NO:41、SEQ ID NO:49、SEQ ID NO:57、SEQ ID NO:23、SEQ ID NO:31、SEQ ID NO:39、SEQ ID NO:47、SEQ ID NO:55或SEQ IDNO:63或各自的互补序列具有至少约95%、优选至少约96%、优选至少约97%、优选至少约98%、优选至少约99%、优选至少约99.1%、优选至少约99.2%、优选至少约99.3%、优选至少约99.4%、优选至少约99.5%、优选至少约99.6%、优选至少约99.7%的序列同一性。
本发明还涉及核酸,其优选为分离的核酸,特别是核糖核酸,所述分离的核酸包含根据SEQ ID NO:11、SEQ ID NO:19、SEQ ID NO:27、SEQ ID NO:35、SEQ ID NO:43、SEQ IDNO:51、SEQ ID NO:59、SEQ ID NO:13、SEQ ID NO:21、SEQ ID NO:29、SEQ ID NO:37、SEQ IDNO:45、SEQ ID NO:53或SEQ ID NO:61的核酸序列或与SEQ ID NO:11、SEQ ID NO:19、SEQID NO:27、SEQ ID NO:35、SEQ ID NO:43、SEQ ID NO:51、SEQ ID NO:59、SEQ ID NO:13、SEQID NO:21、SEQ ID NO:29、SEQ ID NO:37、SEQ ID NO:45、SEQ ID NO:53或SEQ ID NO:61互补的核酸序列、特别是核糖核酸序列,或由所述核酸序列组成。本发明还涉及分离的蛋白或肽,其与SEQ ID NO:11、SEQ ID NO:19、SEQ ID NO:27、SEQ ID NO:35、SEQ ID NO:43、SEQID NO:51、SEQ ID NO:59、SEQ ID NO:13、SEQ ID NO:21、SEQ ID NO:29、SEQ ID NO:37、SEQID NO:45、SEQ ID NO:53或SEQ ID NO:61或各自的互补序列具有至少约95%、优选至少约96%、优选至少约97%、优选至少约98%、优选至少约99%、优选至少约99.1%、优选至少约99.2%、优选至少约99.3%、优选至少约99.4%的序列同一性。
根据SEQ ID NO:2和SEQ ID NO:4的核酸序列各自优选地编码淋巴细胞性脉络丛脑膜炎病毒突变体的糖蛋白,特别是糖蛋白的蛋白组分或蛋白部分。
根据SEQ ID NO:6的核酸序列优选地编码淋巴细胞性脉络丛脑膜炎病毒突变体的L-蛋白。
SEQ ID NO:8的核酸序列优选地编码野生型淋巴细胞性脉络丛脑膜炎病毒的L-蛋白。
关于所述分离的核酸的进一步特征和优点,为了避免重复,也完全参考前面的描述,特别是在本发明的第二和第三方面的上下文中所作的说明。其中所述的特征和优点,特别是关于核酸、特别是核糖核酸的特征和优点,(加以必要的修正)也适用于根据本发明第六方面的所述分离的核酸。
根据第七方面,本发明涉及含有至少一种根据本发明第五方面的核酸、特别是核糖核酸的分离的基因簇或操纵子。
关于所述基因簇或操纵子的进一步特征和优点,为了避免重复,也完全参考前面的描述,特别是在本发明第六方面的上下文中所作的说明。其中所述的特征和优点,特别是关于核酸、特别是核糖核酸的特征和优点,(加以必要的修正)也适用于根据本发明第七方面的分离的基因簇或操纵子。
根据第八方面,本发明涉及含有至少一种根据本发明第六方面的核酸或根据本发明第七方面的基因簇或操纵子的表达载体。
关于所述表达载体的其它特征和优点,为了避免重复,也完全参考本说明书,特别是根据本发明第六和第七方面做出的说明。其中所述的特征和优点,特别是关于核酸和基因簇或操纵子的特征和优点,(加以必要的修正)也适用于根据本发明第八方面的所述表达载体。
根据第九方面,本发明涉及表达或包含根据本发明第五方面的蛋白或肽和/或包含根据本发明第六方面的核酸、特别是核糖核酸的生物体、病毒、载体或质粒。
所述生物体可以是宿主细胞、真菌或细菌。
所述宿主细胞例如可以是真核或原核细胞。此外,所述宿主细胞可以是可用于生产生物体和/或载体和/或质粒的细胞。
所述细菌可以是例如疫苗载体或另一种治疗性细菌。
所述病毒可以是例如疫苗载体或另一种治疗性病毒。
关于所述宿主细胞的其它特征和优点,为了避免重复,也完全参考本说明书,特别是在本发明的第五和第六方面所作的说明。此处所述的特征和优点,特别是关于所述蛋白或肽(特别是糖蛋白)和核酸(特别是核糖核酸的特征和优点,(加以必要的修正)也适用于根据本发明第九方面的宿主细胞。
本发明的其它特征和优点由下面对以实施例方式呈现的优选实施方案的描述、相应的附图和权利要求中得到。下面描述的实施方案仅仅是为了提供对本发明的进一步描述和更好的理解,而不应当解释为限制。
本发明还涉及包含本文公开的LCMV、优选本文公开的LCMV突变体的药物组合物。所述组合物还可以包含药学上可接受的赋形剂。所述药物组合物还可包含检查点阻断剂如PD-1(编程性细胞死亡蛋白1)和/或细胞凋亡调节剂,特别是细胞凋亡抑制剂如SMAC-模拟物(LCL-161)。所述药物组合物可进一步包含药学上可接受的载体。所述载体可以选自水、水性盐水溶液、水性缓冲溶液、细胞培养基和至少两种上述载体的组合。
本发明还涉及本文公开的LCMV、优选本文公开的LCMV突变体在制备药剂中的用途。所述药剂可用于治疗肿瘤。所述药剂可以是根据本发明第四方面的药剂。
本发明还涉及一种治疗肿瘤的方法,所述方法包括给予有此需要的受试者有效量的本文公开的LCMV,优选本文公开的LCMV突变体,或本文公开的药剂,或本文公开的药物组合物。
除非另有说明,在一系列要素之前的术语“至少”应理解为是指该系列中的每个要素。本领域技术人员将认识到或能够使用不超过常规实验来确定与本文所述的本发明的特定实施方案相当的许多等同物。这些等同物意欲包括在本发明中。
本文无论何处所用的术语“和/或”包括“和”、“或”以及“由所述术语连接的要素的全部或任何其它组合”的意思。
本文使用的术语“约”或“近似地”是指在给定值或范围的20%内,优选在10%内,更优选在5%内。然而,它也包括所述具体的数字,例如约20包括20。
除非上下文另有要求,否则贯穿本说明书和随后的权利要求书,措辞“包含(comprise)”和变形,例如“包含(comprises)”和“包含(comprising)”将被理解为意味着包括所述整数或步骤或整数组或步骤组,但不排除任何其它整数或步骤或整数组或步骤组。当用于本文时,术语“包含(comprising)”可被术语“含有(containing)”或“包括(including)”替代,或者有时当用于本文时被术语“具有(having)”替代。
当在本文中使用时,“由……组成(consisting of)”排除了要求限定的要素中未指定的任何元素、步骤或成分。当在本文中使用时,“基本上由……组成”并不排除在本质上不影响权利要求的基本特征和新颖性特征的材料或步骤。
在本文的每种情况下,术语“包含(comprising)”、“基本上由……组成(consisting essentially of)”和“由……组成(consisting of)”中的任何一个可以用另外两个术语中的任一个代替。例如术语“包含(comprising)”意指也为“基本上由……组成(consisting essentially of)”和“由……组成(consisting of)”提供明确的支持,术语“基本上由……组成(consisting essentially of)”意指也为“包含(comprising)”和“由……组成(consisting of)”提供明确的支持,术语“由……组成(consisting of)”意指也为“基本上由……组成(consisting essentially of)”和“包含(comprising)”提供明确的支持。
应当理解,本发明不限于本文所述的具体方法、方案、材料、试剂和物质等,因此可以变化。这里使用的术语仅是为了描述特定的实施方案,而不是为了限制本发明的范围,本发明的范围仅由权利要求限定。
本说明书全文中引用的所有出版物(包括所有专利、专利申请、科学出版物、制造商说明书、说明书等)在此全文引入作为参考。这里的任何内容都不应被解释为是对本发明由于现有发明而没有资格先于这种公开的认可。在引入作为参考的材料与本说明书相矛盾或不一致的情况上,本说明书将替代任何这样的材料。
实施例
1.方法和材料
1.1小鼠
对于体内抗肿瘤分析,使用WT动物(C57BL/6背景)或没有适应性免疫系统的NOD.SCID小鼠。OT-1小鼠作为转基因小鼠,携带卵清蛋白特异性MHC-I限制性T细胞受体。
1.2细胞系
MC57(CVCL_4985)是鼠成纤维细胞系,沙粒病毒LCMV在其中能很好地增殖。C643(CVCL_5969)是人未分化甲状腺癌细胞系。H1975是人肺癌细胞系(CVCL_1511,ATCC,CRL-5908,腺癌)。TrampC2是鼠腺癌细胞系(CVCL_3615)。MOPC是鼠口咽细胞系。CMT167(CVCL_2405)是鼠肺癌细胞系。B16F10-OVA是表达作为模型抗原的卵清蛋白的鼠黑色素瘤细胞系(CVCL_0159)。UKE-Mel-13a是从人黑色素瘤转移瘤中分离的原代肿瘤细胞,其传代少于100次。511950是从转基因鼠胰腺癌中分离的原代肿瘤细胞(Mazur PK等人,Nat Med.2015年十月;21(10):1163-71。),并且传代少于20次。511950R来源于511950细胞,在MEK抑制剂曲美替尼的处理下传代少于100次。
1.3病毒
LCMV毒株WE获自Zinkemagel教授的实验室(实验免疫学,苏黎世,瑞士),并且自2008年起在L929细胞或BHK细胞中繁殖。克隆LCMV-P42、LCMV-P52和LCMV-P91在不同代后分离并测序。
1.4试剂
LCL161(Selleckchem)和抗-PD1(BioXcell)分别与LCMV和LCMV-P52组合测试其抗肿瘤活性。
1.5通过免疫荧光检测LCMV感染的细胞
使用免疫荧光检测细胞中的LCMV。将细胞接种在24孔板中,每个孔包含一个盖玻片。24小时后,用LCMV感染细胞,24小时后用荧光色素标记的抗LCMV-NP抗体(克隆VL4)染色,用荧光显微镜观察并用集成的CCD相机拍照。
1.6通过噬菌斑测定法测定上清液中的LCMV
为了确定细胞的LCMV生产,将细胞接种在24孔板中,24小时后用LCMV感染。24小时后提取上清液。将所述上清液滴到24孔板中,加入MC57细胞(150,000个细胞/孔)。4小时后加入甲基纤维素。再过48小时后,用抗LCMV-NP抗体(克隆KL53)分析细胞坪中的LCMV斑。斑块计数以确定上清液中每毫升中的感染性颗粒的数量。
1.7病毒的传代
为了使病毒适应肿瘤,用LCMV-WE感染不同的原代肿瘤细胞或肿瘤细胞系。细胞在24孔板中铺板(1ml培养基中约100,000个细胞/孔)。24小时后,加入100μL感染复数(MOI)=1的病毒。在1-30分钟之间(取决于设置)除去初始培养液并加入新培养基。24或48或72小时后,提取细胞培养上清液并冷冻留待进一步分析。用100微升(micorL)所述提取的上清液感染新铺板的细胞。该过程重复30-100次。
1.8测序
病毒RNA反转录后,在聚合酶链反应(PCR)中用序列特异性引物对(寡核苷酸)扩增cDNA。PCR产物纯化、通过循环测序(改进的singer方法)测序,通过毛细管电泳分离产物,并且序列记录为电泳图谱。翻译核酸序列以获得蛋白质序列。
1.9天然免疫激活
使用鼠IFN-αELISA(Thermofisher)通过生物标志物IFN-α测定LCMV激活天然免疫系统的能力。
1.10适应性免疫激活
通过活化的淋巴细胞的四聚体染色(NIH,Tetramer Facility)测试LCMV激活适应性免疫系统的能力。
1.11肿瘤生长和治疗
为测量抗肿瘤效果,5×10
1.12卵清蛋白(肿瘤)特异性CD8+ T细胞的分离和转移
为分析肿瘤特异性CD8
1.13肿瘤特异性CD8+ T细胞的测量
为分析肿瘤特异性CD8
1.14统计学分析
采用未配对的双样本Student’s t-检验比较平均值。数据以平均值±SEM表示。统计显著性的水平被确定为p<0.05。
1.15 LCMV-P42的产生:
LCMV-WE在原代肿瘤细胞培养物(UKE-Mel-13a)中传代42次。42次传代后,在新病毒(LCMV-P42)中检测到功能性突变。LCMV-WE和突变体P42的核酸和氨基酸序列如图25(A和B)所示。
1.16 LCMV-P91、LCMV-P52及其亚克隆的产生:
LCMV-WE在肿瘤细胞系H1975中传代52次。52次传代后,在新病毒的糖蛋白中检测到突变I181M和R185W。此外,发现了一些最可能是不相关和/或寡克隆突变(准种)。该病毒命名为:“LCMV-P52”。为了确定突变I181M和R185W的稳定性和重要性,将P52代的上清液再传代39次。衍生自该代的病毒命名为“LCMV-P91”,并且仍然包含突变I181M和R185W。通过限制稀释亚克隆病毒LCMV-P52。该克隆病毒命名为“LCMV-P52.1”。突变I181M和R185W保持稳定。所述被认为不相关的和/或寡克隆的突变(准种)显示出一些变化。为了确定单突变I181M和R185W的作用,分析了一些早些的代。P29代包含具有单独的I181M和R185W突变的病毒。通过限制稀释亚克隆来自P29代的病毒。具有单一突变R185W的一个亚克隆命名为:“LCMV-P52-1.3”;具有单一突变I181M的一个亚克隆命名为:“LCMV-P52-2.1”。LCMV突变体P52、P92、P52-1、P52-1.3和P52-2.1的核酸和氨基酸序列如图25(C-G)所示。LCMV-WE与突变体P42、P52、P92、P52-1、P52-1.3和P52-2.1核酸和氨基酸序列的比对在图26(A-H)中示出。
2.研究
2.1用LCMV(毒株WE,MOI 1)感染肿瘤细胞系MC57、C643、H1975和原代肿瘤细胞培养物(UKE Mel-13a)。24小时后测量复制(n=3)。
由此证明LCMV(毒株WE)扩散情况不同。与肿瘤细胞系MC57相比,在细胞系C643和H1975以及原代肿瘤细胞培养物(UKE-Mel-13a)中扩散减少。所得结果以图形方式在图1中示出。
在MC57、C643、H1975和UKE-Mel-13a的培养物中可以看到白色的LCMV感染的细胞。φ=未感染,LCMV=LCMV感染。
2.2用LCMV(毒株WE,MOI 1)感染肿瘤细胞系MC57和原代肿瘤细胞培养物511950(左图)。用LCMV(毒株WE,MOI 1)感染肿瘤细胞系MC57、Tramp-C2和原代肿瘤细胞培养物(511950和511950R)(右图)。24小时后测量上清液中感染性病毒颗粒的数量。
由此证明与MC57肿瘤细胞系相比,LCMV(毒株WE)在Tramp-C2细胞系以及原代肿瘤细胞培养物(511950和511950R)中增殖较少。结果在图2中示出。
图2的图例如下:
纵坐标:上清液中的感染性LCMV颗粒(PFU/mL),
横坐标:治疗组;MC57、Tramp-C2、511950、511950R。
2.3 LCMV-WE在原代肿瘤细胞培养物(UKE-Mel-13a)中传代42次。42次传代后,在新病毒(LCMV-P42)中检测到功能性突变。
由此可以证明原代肿瘤细胞适用于通过传代修饰沙粒病毒。实验过程在图3中示出。
2.4 LCMV-WE在肿瘤细胞系H1975中传代52次。52次传代后,在新病毒LCMV-P52中检测到功能性突变。
由此以H1975为例,证明具有减少的LCMV复制(与细胞系MC57相比)的肿瘤细胞系适用于通过传代改造沙粒病毒。实验过程在图4中示出。
2.5 LCMV-P52在肿瘤细胞系H1975中传代39次。39次传代后,在新病毒LCMV-P91中检测到更多的功能性突变。
由此证明H1975细胞能够通过传代改造沙粒病毒。实验过程以图形方式在图5中示出。
2.6用LCMV-WE和LCMV-P52(MOI 1)感染细胞系H1975。12小时后测定在上清液中的病毒(n=6)。
由此证明LCMV-P52在H1975细胞中的复制优于LCMV-WE。所得结果以图表形式在图6中示出。
图6的图例如下:
纵坐标:上清液中的感染性LCMV颗粒(PFU/mL),
横坐标:治疗组;LCMV-WE或LCMV-P52
2.7用LCMV-WE和LCMV-P52(MOI 1)感染源自鼠骨髓的树突细胞。24小时后测定在上清液中的病毒(n=3)。
由此证明LCMV-P52在抗原呈递细胞中的复制优于LCMV-WE。所得结果以图表形式在图7中示出。
图7的图例如下:
纵坐标:上清液中的感染性LCMV颗粒(PFU/mL),
横坐标:治疗组;LCMV-WE或LCMV-P52
2.8用LCMV-WE或LCMV-P52(MOI 1)感染肿瘤细胞系H1975。24小时后,通过免疫荧光测量病毒扩散。
由此以H1975为例,证明与LCMV-WE相比,LCMV-P52能更好地在肿瘤细胞系扩散。所得结果以图形形式在图8中示出。
显示为白色的是LCMV-WE或LCMV-P52感染的培养物中被LCMV感染的细胞。
2.9用LCMV-WE或LCMV-P52(MOI 1)感染原代肿瘤细胞(UKE-Mel-13a)。24小时后通过免疫荧光测量病毒的扩散。
由此证明与LCMV-WE相比,LCMV-P52能更好地在原发性肿瘤细胞中扩散。所得结果在以图形形式在图9中示出。
LCMV-WE或LCMV-P52感染的培养物中被LCMV感染的细胞显示为白色。
2.10用LCMV-WE或LCMV-P52(2×10
由此证明LCMV-P52比LCMV-WE引起更强的天然免疫激活。所得结果以图表形式在图10中示出。
图10的图例如下:
纵坐标:IFN-α浓度(ng/mL血清)
横坐标:治疗组;LCMV-WE或LCMV-P52感染的动物。
2.11用LCMV-WE或LCMV-P52(2×10
由此证明LCMV-P52比LCMV-WE诱导更强的适应性免疫激活。所得结果以图表形式在图11中示出。
图11的图例如下:
纵坐标:病毒特异性CD8+ T细胞(占血液中总CD8+ T细胞的%),
横坐标:时间(感染后天数)。
2.12 NOD.SCID小鼠皮下注射5×10
由此证明用LCMV-P52治疗比用LCMV-WE治疗具有更强的抗肿瘤作用。所得结果以图表形式在图12中示出。
图12的图例如下:
纵坐标:平均肿瘤直径(cm),
横坐标:时间(LCMV治疗后天数)
2.13 C57BL/6小鼠皮下注射5×10
由此证明用LCMV-P52治疗具有强的抗肿瘤作用。所得结果以图表形式在图13中示出。
图13的图例如下:
纵坐标:肿瘤体积(mm
横坐标:时间(LCMV治疗后天数)
2.14 C57BL/6小鼠皮下注射5×10
由此证明用LCMV-P52治疗具有强的抗肿瘤作用。所得结果以图表形式在图14中示出。
图14的图例如下:
纵坐标:肿瘤体积(mm
横坐标:时间(LCMV治疗后天数)
由此证明用LCMV-P52治疗具有强的抗肿瘤作用。所得结果以图形形式在图15中示出。
在肺中的肿瘤细胞以黑色示出;φ=未感染
2.15 C57BL/6小鼠静脉注射5×10
φ=对照动物,每组4个肺;LCMV-P52=用LCMV-P52治疗,每组4个肺。
2.16 C57BL/6小鼠静脉注射5×10
由此证明用LCMV-P52治疗增强肿瘤特异性CD8+ T细胞的扩增。所得结果以图表形式在图16中示出。
图16的图例如下:
纵坐标:血液中肿瘤特异性CD8+ T细胞的频率(占总CD8+ T细胞的%)
横坐标:治疗组φ=未感染,LCMV-P52=用LCMV-P52治疗
2.17 C57BL/6小鼠静脉注射5×10
由此证明用LCMV-P52治疗增强肿瘤特异性CD8+ T细胞的功能。所得结果以图表形式在图17中示出。
图17的图例如下:
纵坐标:产生IFN-γ的肿瘤特异性CD8+ T细胞的频率(占总CD8+ T细胞的%)
横坐标:治疗组;φ:未用LCMV-P52治疗;LCMV-P52:用LCMV-P52治疗;图例:-:未用抗原;+:用抗原(SIINFEKL肽)再刺激。
2.18 C57BL/6小鼠皮下注射5×10
由此证明用LCMV-WE治疗与LCl-161具有协同作用。所得结果以图表形式在图18中示出。
图18的图例如下:
纵坐标:肿瘤体积(mm
横坐标:时间(LCMV给药后天数)
2.19 C57BL/6小鼠皮下注射5×10
可显示用LCMV-WE治疗与LCl-161具有协同作用。所得结果以图表形式在图19中示出。
图19的图例如下:
纵坐标:动物的存活率(%),
横坐标:时间(LCMV给药后天数)
2.20 C57BL/6小鼠皮下注射5×10
由此证明用LCMV-P52治疗与检查点阻断剂(例如抗-PD-1)具有协同作用。所得结果以图表形式在图20中示出。
图20的图例如下:
纵坐标:肿瘤体积(mm
横坐标:时间(LCMV治疗后天数)
本说明书中提到的氨基酸和核酸序列对应于下面序列表中公开的氨基酸和核酸序列。
2.21将10
数据表明突变I181M和R185W分别增加肿瘤细胞中的病毒繁殖。
图21的图例如下:
X轴:不同的病毒
Y轴:上清液中的LCMV(log
2.22将2.5×10
数据表明突变I181M或突变185W增加HCC1954肿瘤细胞中的病毒繁殖。
图22的图例如下:
X轴:不同的病毒
Y轴:上清液中的LCMV(log
2.23鼠胰腺癌细胞(511950,4×10
数据表明突变I181M引起肿瘤细胞中病毒繁殖增加。
图23的图例如下:
X轴:不同的细胞类型
Y轴:上清液中的LCMV(log
2.24 C57BL/6小鼠经静脉感染2×10
数据表明突变I181M和R185W增加LCMV刺激特异性T细胞的能力。突变I181M和R185W的组合可能对早期T细胞刺激具有协同性能。
图24的图例如下:
X轴:不同的病毒
Y轴:四聚体-GP33-结合的CD8
本文中说明性描述的本发明可以在缺少未在本文中具体公开的一个或多个要素、一种或多种限制的情况下合适地被实施。另外,本文所用的术语和表达已经被用作描述的术语,而不是用作限制,并且在使用这样的术语和表达时并不意味着排除所示和所述特征或其部分的任何等同物,而是应该认识到在所要求保护的本发明的范围内可以进行各种改进。因此,应当理解,尽管本发明已经由示例性实施方案和可选的特征具体公开,但本领域技术人员可以采用本文公开的在其中实施的本发明的改进和变形,并且这种改进和变形被认为是在本发明的范围内。
本发明在此被大体上和一般性地描述。属于通用披露内容的较狭义类型和亚属组中的每一个也形成本发明的一部分。这包括本发明的通用说明,其限制条件或负面限制是从所述属中移除任何标的物,无论所删除的材料是否在本文中特定叙述。
序列表
<110> 阿巴洛斯治疗有限公司
<120> 用于制备抗肿瘤沙粒病毒的方法以及沙粒病毒突变体
<130> LC21310004P
<150> DE 10 2018 215 551.8
<151> 2018-09-12
<160> 64
<170> PatentIn版本3.5
<210> 1
<211> 498
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒
<220>
<221> MISC_FEATURE
<223> 淋巴细胞性脉络丛脑膜炎病毒突变体p52糖蛋白;ssrna
双义-链病毒;沙粒病毒科;沙粒病毒;旧大陆沙粒病毒
<400> 1
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Pro Gln Ser Ala Met Ser Gln Cys Trp Thr Phe Arg Gly Arg Val Leu
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Asp Met Phe Arg Thr Ala Phe Gly Gly Lys Tyr Met Arg Ser Gly Trp
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Gly Trp Ala Gly Ser Asp Gly Lys Thr Thr Trp Cys Ser Gln Thr Ser
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Tyr Gln Tyr Leu Ile Ile Gln Asn Arg Thr Trp Glu Asn His Cys Arg
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Tyr Ala Gly Pro Phe Gly Met Ser Arg Ile Leu Phe Ala Gln Glu Lys
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<210> 2
<211> 1497
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒
<220>
<221> MISC_FEATURE
<223> 淋巴细胞性脉络丛脑膜炎病毒突变体p52糖蛋白;ssrna
双义-链病毒;沙粒病毒科;沙粒病毒;旧大陆沙粒病毒
<400> 2
atgggtcaga ttgtgacaat gtttgaggct ttgcctcaca tcattgatga ggtcatcaac 60
attgtcatta ttgtgctcat tataatcacg agcatcaaag ctgtgtacaa tttcgccacc 120
tgtgggatat tagcactggt cagcttcctt tttttggctg gtaggtcctg tggcatgtac 180
ggccttaatg gtcccgacat ctataaaggg gtttaccagt tcaaatcagt ggagtttgat 240
atgtctcact taaatctgac gatgcccaat gcgtgctcag ccaacaactc tcatcactac 300
atcagtatgg gaagctctgg actggagcta actttcacta acgactccat ccttaatcac 360
aatttttgca acttaacctc cgctttcaac aaaaagactt ttgaccatac actcatgagt 420
atagtctcga gtctgcacct cagtattaga gggaattcca accacaaagc agtgtcttgt 480
gattttaaca atggcatcac cattcaatac aacttgtcat tttcggaccc acagagcgct 540
atgagccagt gttggacttt cagaggtaga gtcttggaca tgtttagaac tgcctttgga 600
ggaaaataca tgagaagtgg ctggggctgg gcaggttcag atggcaagac cacttggtgc 660
agccaaacaa gctatcagta cctaatcata caaaacagga cttgggaaaa ccactgtaga 720
tatgcaggcc cttttgggat gtctagaatc ctctttgctc aggaaaagac aaagtttctc 780
actaggagac ttgcaggcac attcacctgg accctgtcag actcctcagg agtagaaaat 840
ccaggtggtt attgcctgac caaatggatg atccttgctg cagagctcaa atgttttggg 900
aatacagctg ttgcaaaatg taatgtcaat catgatgaag agttctgtga catgctacga 960
ctaattgatt acaacaaggc cgccctgagt aagttcaagc aagatgtaga gtctgccttg 1020
catgtattca aaacaacagt aaattctctg atttccgatc agctgttgat gaggaatcat 1080
ctaagagatc taatgggggt accatactgt aattactcaa agttctggta tctggaacat 1140
gctaagactg gtgagactag tgtacccaag tgctggcttg tcactaatgg ctcctacttg 1200
aatgagaccc actttagtga tcaaatcgaa caagaagcag ataacatgat cacagagatg 1260
ttgaggaagg actacataaa aagacaaggg agtactcctt tagccttaat ggatcttttg 1320
atgttttcaa catcagcata tctaatcagc atctttctgc atcttgtgaa gataccaaca 1380
catagacaca taaagggcgg ttcatgtcca aagccacacc gcttgaccaa caaggggatc 1440
tgtagttgtg gtgcattcaa ggtgcctggt gtaaaaacta tctggaaaag acgctga 1497
<210> 3
<211> 498
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒
<220>
<221> MISC_FEATURE
<223> 淋巴细胞性脉络丛脑膜炎病毒突变体p42糖蛋白;ssrna
双义-链病毒;沙粒病毒科;沙粒病毒;旧大陆沙粒病毒
<400> 3
Met Gly Gln Ile Val Thr Met Phe Glu Ala Leu Pro His Ile Ile Asp
1 5 10 15
Glu Val Ile Asn Ile Val Ile Ile Val Leu Ile Ile Ile Thr Ser Ile
20 25 30
Lys Ala Val Tyr Asn Phe Ala Thr Cys Gly Ile Leu Ala Leu Val Ser
35 40 45
Phe Leu Phe Leu Ala Gly Arg Ser Cys Gly Met Tyr Gly Leu Asn Gly
50 55 60
Pro Asp Ile Tyr Lys Gly Val Tyr Gln Phe Lys Ser Val Glu Phe Asp
65 70 75 80
Met Ser His Leu Asn Leu Thr Met Pro Asn Ala Cys Ser Ala Asn Asn
85 90 95
Ser His His Tyr Ile Ser Met Gly Ser Ser Gly Leu Glu Leu Thr Phe
100 105 110
Thr Asn Asp Ser Ile Leu Asn His Asn Phe Cys Asn Leu Thr Ser Ala
115 120 125
Phe Asn Lys Lys Thr Phe Asp His Thr Leu Met Ser Ile Val Ser Ser
130 135 140
Leu His Leu Ser Ile Arg Gly Asn Ser Asn His Lys Ala Val Ser Cys
145 150 155 160
Asp Phe Asn Asn Gly Ile Thr Ile Gln Tyr Asn Leu Ser Phe Ser Asp
165 170 175
Pro Gln Ser Ala Met Ser Gln Cys Arg Thr Phe Arg Gly Arg Val Leu
180 185 190
Asp Met Phe Arg Thr Ala Phe Gly Gly Lys Tyr Met Arg Ser Gly Trp
195 200 205
Gly Trp Ala Gly Ser Asp Gly Lys Thr Thr Trp Cys Ser Gln Thr Ser
210 215 220
Tyr Gln Tyr Leu Ile Ile Gln Asn Arg Thr Trp Glu Asn His Cys Arg
225 230 235 240
Tyr Ala Gly Pro Phe Gly Met Ser Arg Ile Leu Phe Ala Gln Glu Lys
245 250 255
Thr Lys Phe Leu Thr Arg Arg Leu Ala Gly Thr Phe Thr Trp Thr Leu
260 265 270
Ser Asp Ser Ser Gly Val Glu Asn Pro Gly Gly Tyr Cys Leu Thr Lys
275 280 285
Trp Met Ile Leu Ala Ala Glu Leu Lys Cys Phe Gly Asn Thr Ala Val
290 295 300
Ala Lys Cys Asn Val Asn His Asp Glu Glu Phe Cys Asp Met Leu Arg
305 310 315 320
Leu Ile Asp Tyr Asn Lys Ala Ala Leu Ser Lys Phe Lys Gln Asp Val
325 330 335
Glu Ser Ala Leu His Val Phe Lys Thr Thr Val Asn Ser Leu Ile Ser
340 345 350
Asp Gln Leu Leu Met Arg Asn His Leu Arg Asp Leu Met Gly Val Pro
355 360 365
Tyr Cys Asn Tyr Ser Lys Phe Trp Tyr Leu Glu His Ala Lys Thr Gly
370 375 380
Glu Thr Ser Val Pro Lys Cys Trp Leu Val Thr Asn Gly Ser Tyr Leu
385 390 395 400
Asn Glu Thr His Phe Ser Asp Gln Ile Glu Gln Glu Ala Asp Asn Met
405 410 415
Ile Thr Glu Met Leu Arg Lys Asp Tyr Ile Lys Arg Gln Gly Ser Thr
420 425 430
Pro Leu Ala Leu Met Asp Leu Leu Met Phe Ser Thr Ser Ala Tyr Leu
435 440 445
Ile Ser Ile Phe Leu His Leu Val Lys Ile Pro Thr His Arg His Ile
450 455 460
Lys Gly Gly Ser Cys Pro Lys Pro His Arg Leu Thr Asn Lys Gly Ile
465 470 475 480
Cys Ser Cys Gly Ala Phe Lys Val Pro Gly Val Lys Thr Ile Trp Lys
485 490 495
Arg Arg
<210> 4
<211> 1497
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒
<220>
<221> MISC_FEATURE
<223> 淋巴细胞性脉络丛脑膜炎病毒突变体p42糖蛋白;ssrna
双义-链病毒;沙粒病毒科;沙粒病毒;旧大陆沙粒病毒
<400> 4
atgggtcaga ttgtgacaat gtttgaggct ttgcctcaca tcattgatga ggtcatcaac 60
attgtcatta ttgtgctcat tataatcacg agcatcaaag ctgtgtacaa tttcgccacc 120
tgtgggatat tagcactggt cagcttcctt tttttggctg gtaggtcctg tggcatgtac 180
ggccttaatg gtcccgacat ctataaaggg gtttaccagt tcaaatcagt ggagtttgat 240
atgtctcact taaatctgac gatgcccaat gcgtgctcag ccaacaactc tcatcactac 300
atcagtatgg gaagctctgg actggagcta actttcacta acgactccat ccttaatcac 360
aatttttgca acttaacctc cgctttcaac aaaaagactt ttgaccatac actcatgagt 420
atagtctcga gtctgcacct cagtattaga gggaattcca accacaaagc agtgtcttgt 480
gattttaaca atggcatcac cattcaatac aacttgtcat tttcggaccc acagagcgct 540
atgagccagt gtaggacttt cagaggtaga gtcttggaca tgtttagaac tgcctttgga 600
ggaaaataca tgagaagtgg ctggggctgg gcaggttcag atggcaagac cacttggtgc 660
agccaaacaa gctatcagta cctaatcata caaaacagga cttgggaaaa ccactgtaga 720
tatgcaggcc cttttgggat gtctagaatc ctctttgctc aggaaaagac aaagtttctc 780
actaggagac ttgcaggcac attcacctgg accctgtcag actcctcagg agtagaaaat 840
ccaggtggtt attgcctgac caaatggatg atccttgctg cagagctcaa atgttttggg 900
aatacagctg ttgcaaaatg taatgtcaat catgatgaag agttctgtga catgctacga 960
ctaattgatt acaacaaggc cgccctgagt aagttcaagc aagatgtaga gtctgccttg 1020
catgtattca aaacaacagt aaattctctg atttccgatc agctgttgat gaggaatcat 1080
ctaagagatc taatgggggt accatactgt aattactcaa agttctggta tctggaacat 1140
gctaagactg gtgagactag tgtacccaag tgctggcttg tcactaatgg ctcctacttg 1200
aatgagaccc actttagtga tcaaatcgaa caagaagcag ataacatgat cacagagatg 1260
ttgaggaagg actacataaa aagacaaggg agtactcctt tagccttaat ggatcttttg 1320
atgttttcaa catcagcata tctaatcagc atctttctgc atcttgtgaa gataccaaca 1380
catagacaca taaagggcgg ttcatgtcca aagccacacc gcttgaccaa caaggggatc 1440
tgtagttgtg gtgcattcaa ggtgcctggt gtaaaaacta tctggaaaag acgctga 1497
<210> 5
<211> 2209
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒
<220>
<221> MISC_FEATURE
<223> 淋巴细胞性脉络丛脑膜炎病毒突变体L-蛋白;ssrna
双义-链病毒;沙粒病毒科;沙粒病毒;旧大陆沙粒病毒
<400> 5
Met Asp Glu Thr Ile Ala Asp Leu Arg Glu Leu Cys Leu Asn Tyr Ile
1 5 10 15
Glu Gln Asp Glu Arg Leu Ser Arg Gln Lys Leu Asn Phe Leu Gly Gln
20 25 30
Arg Glu Pro Arg Met Val Leu Ile Glu Gly Leu Lys Leu Leu Ser Arg
35 40 45
Cys Ile Glu Ile Asp Ser Ala Asp Lys Ser Gly Cys Ile His Asn His
50 55 60
Asp Asp Lys Ser Val Glu Thr Ile Leu Ile Asp Ser Gly Ile Val Cys
65 70 75 80
Pro Gly Leu Pro Leu Ile Ile Pro Asp Gly Tyr Lys Leu Ile Asp Asn
85 90 95
Ser Leu Ile Leu Leu Glu Cys Phe Val Arg Ser Thr Pro Ala Ser Phe
100 105 110
Glu Lys Lys Phe Ile Glu Asp Thr Asn Lys Leu Ala Cys Ile Lys Glu
115 120 125
Asp Leu Ala Val Ala Gly Ile Thr Leu Val Pro Ile Val Asp Gly Arg
130 135 140
Cys Asp Tyr Asp Asn Ser Phe Met Pro Glu Trp Val Asn Phe Lys Phe
145 150 155 160
Arg Asp Leu Leu Phe Lys Leu Leu Glu Tyr Ser Ser Gln Asp Glu Lys
165 170 175
Val Phe Glu Glu Ser Glu Tyr Phe Arg Leu Cys Glu Ser Leu Lys Thr
180 185 190
Thr Val Asp Lys Arg Ser Gly Met Asp Ser Met Lys Ile Leu Lys Asp
195 200 205
Ala Arg Ser Phe His Asn Asp Glu Ile Met Lys Met Cys His Asp Gly
210 215 220
Val Asn Pro Asn Met Ser Cys Asp Asp Val Val Phe Gly Ile Asn Ser
225 230 235 240
Phe Phe Gly Arg Phe Arg Arg Asp Leu Leu Asn Gly Lys Leu Lys Arg
245 250 255
Asn Phe Gln Lys Val Ser Pro Gly Gly Leu Ile Lys Glu Phe Ser Glu
260 265 270
Leu Tyr Glu Thr Leu Thr Asp Asn Asp Asp Ile Leu Met Leu Ser Lys
275 280 285
Glu Ala Val Glu Ser Cys Pro Leu Met Arg Phe Ile Thr Ala Glu Thr
290 295 300
His Gly His Glu Arg Gly Ser Asp Ala Asn Thr Glu Tyr Glu Arg Leu
305 310 315 320
Leu Ser Met Leu Asn Lys Val Lys Ser Leu Lys Leu Leu Asn Thr Arg
325 330 335
Arg Arg Gln Leu Leu Asn Leu Asp Val Leu Cys Leu Ser Ser Leu Ile
340 345 350
Lys Gln Ser Ile Ser Lys Gly Leu Glu Asn Asp Lys His Trp Val Gly
355 360 365
Cys Cys Tyr Ser Ser Val Asn Asp Arg Leu Val Ser Leu Gln Ser Thr
370 375 380
Lys Glu Glu Phe Met Arg Leu Leu Lys Asn Arg Arg Lys Ser Arg Val
385 390 395 400
His Lys Lys Ala Ser Leu Asp Glu Leu Phe Arg Val Ser Ile Asn Glu
405 410 415
Phe Ile Ala Lys Ile Gln Lys Cys Leu Ser Thr Val Gly Leu Ser Phe
420 425 430
Glu His Tyr Gly Leu Ser Glu Cys Leu Val Gln Glu Cys His Ile Pro
435 440 445
Phe Ala Glu Phe Glu Asn Phe Met Arg Ala Gly Thr His Pro Val Met
450 455 460
His Tyr Thr Lys Phe Glu Asp Tyr Thr Phe Gln Pro Asn Ile Glu Gln
465 470 475 480
Leu Arg Gly Leu Gln Ser Leu Arg Lys Leu Ser Ser Val Cys Leu Ala
485 490 495
Leu Thr Asn Ser Met Lys Thr Ser Ser Val Ala Arg Leu Arg Gln Asn
500 505 510
Gln Leu Gly Ser Val Arg Tyr Gln Val Val Glu Cys Lys Glu Val Phe
515 520 525
Cys Gln Ile Ile Lys Leu Asp Ser Glu Glu Tyr His Leu Leu Tyr Gln
530 535 540
Lys Thr Gly Glu Ser Ser Arg Cys Tyr Ser Ile Gln Gly Pro Asp Gly
545 550 555 560
His Leu Ile Ser Phe Tyr Ala Asp Pro Lys Arg Phe Phe Leu Pro Ile
565 570 575
Phe Ser Asp Glu Val Leu His Asn Met Ile Asp Thr Met Ile Ser Trp
580 585 590
Ile Arg Ser Cys Pro Asp Leu Lys Asp Ser Leu Ile Asp Ile Glu Thr
595 600 605
Ala Leu Arg Thr Leu Ile Leu Leu Met Leu Thr Asn Pro Thr Lys Arg
610 615 620
Asn Gln Lys Gln Val Gln Asn Ile Arg Tyr Leu Val Met Ala Ile Val
625 630 635 640
Ser Asp Phe Ser Ser Thr Ser Leu Met Asp Lys Leu Lys Glu Asp Leu
645 650 655
Ile Thr Pro Ala Glu Lys Val Val Tyr Arg Leu Leu Arg Phe Leu Ile
660 665 670
Arg Thr Ile Phe Gly Thr Gly Glu Lys Val Leu Leu Ser Ala Lys Phe
675 680 685
Lys Phe Met Leu Asn Val Ser Tyr Leu Cys His Leu Ile Thr Lys Glu
690 695 700
Thr Pro Asp Arg Leu Thr Asp Gln Ile Lys Cys Phe Glu Lys Phe Phe
705 710 715 720
Glu Pro Lys Ser Glu Phe Gly Phe Phe Val Asn Pro Lys Glu Thr Ile
725 730 735
Thr Pro Glu Glu Glu Cys Val Phe Tyr Glu Gln Met Lys Lys Phe Thr
740 745 750
Gly Lys Asp Ile Asp Cys Gln His Ser Thr Pro Gly Val Asn Leu Glu
755 760 765
Ile Phe Ser Met Met Val Ser Ser Phe Asn Asn Gly Thr Leu Ile Leu
770 775 780
Lys Gly Glu Lys Arg Leu Asn Asn Leu Asp Pro Met Thr Asn Ser Gly
785 790 795 800
Cys Ala Thr Ala Leu Asp Leu Ala Ser Asn Lys Ser Val Val Val Asn
805 810 815
Lys His Leu Asn Gly Glu Arg Leu Leu Glu Tyr Asp Phe Asn Lys Leu
820 825 830
Leu Val Ser Ala Val Ser Gln Ile Thr Glu Gly Phe Met Arg Lys Gln
835 840 845
Lys Tyr Lys Leu Arg His Ser Asp Tyr Glu Tyr Lys Val Ser Lys Leu
850 855 860
Val Ser Arg Leu Val Ile Gly Ser Arg Lys Thr Glu Val Asp Lys Leu
865 870 875 880
Glu Asp Asp Pro Val Asp Val Cys Phe Glu Gly Glu Glu Glu Thr Ser
885 890 895
Phe Phe Arg Ser Leu Glu Asp Lys Val Ser Ser Thr Ile Thr Arg Tyr
900 905 910
Asn Arg Gly Thr Arg Leu Asn Glu Gly Gln Gly Glu Gly Glu Phe Lys
915 920 925
Asn Thr Lys Gly Leu His His Leu Gln Ile Ile Leu Ser Gly Lys Arg
930 935 940
Ala Tyr Leu Arg Lys Val Ile Leu Ser Glu Ile Ser Phe His Leu Val
945 950 955 960
Glu Asp Phe Asp Pro Ser Cys Leu Thr Asn Asp Asp Met Arg Phe Ile
965 970 975
Cys Glu Ala Val Glu Gly Ser Thr Glu Leu Ser Pro Leu Tyr Phe Thr
980 985 990
Ser Ala Val Lys Glu Gln Cys Gly Leu Asp Glu Met Ala Arg Asn Leu
995 1000 1005
Cys Arg Lys Phe Phe Ser Glu Gly Asp Trp Phe Ser Cys Met Lys
1010 1015 1020
Met Ile Leu Leu Gln Met Asn Ala Asn Ala Tyr Ser Gly Lys Tyr
1025 1030 1035
Arg His Met Gln Arg Gln Ser Leu Asn Phe Lys Phe Asp Trp Asp
1040 1045 1050
Lys Leu Glu Glu Asp Val Arg Ile Ser Glu Arg Glu Ser Asn Ser
1055 1060 1065
Glu Ser Leu Ser Lys Ala Leu Ser Leu Thr Lys Cys Met Ser Ala
1070 1075 1080
Ala Leu Lys Asn Leu Cys Phe Tyr Ser Glu Glu Ser Pro Thr Ser
1085 1090 1095
Tyr Thr Ser Val Gly Pro Asp Ser Gly Arg Leu Lys Phe Ala Leu
1100 1105 1110
Ser Tyr Lys Glu Gln Val Gly Gly Asn Arg Glu Leu Tyr Ile Gly
1115 1120 1125
Asp Leu Arg Thr Lys Met Phe Thr Arg Leu Val Glu Asp Tyr Phe
1130 1135 1140
Glu Ser Phe Ser Ser Phe Phe Ser Gly Ser Cys Leu Asn Asn Asp
1145 1150 1155
Lys Glu Phe Glu Asn Ala Ile Leu Ser Met Thr Ile Asn Val Arg
1160 1165 1170
Glu Gly Leu Leu Asn Tyr Ser Met Asp His Ser Lys Trp Gly Pro
1175 1180 1185
Met Met Cys Pro Phe Leu Phe Leu Met Leu Leu Gln Asn Leu Lys
1190 1195 1200
Leu Gly Asp Asp Gln Tyr Val Arg Ser Gly Lys Asp His Val Ser
1205 1210 1215
Thr Leu Leu Thr Trp His Met His Lys Leu Val Glu Val Pro Phe
1220 1225 1230
Pro Val Val Asn Ala Met Met Lys Ser Tyr Val Lys Ser Lys Leu
1235 1240 1245
Lys Leu Leu Lys Gly Ser Gly Thr Thr Val Thr Glu Arg Ile Phe
1250 1255 1260
Arg Glu Tyr Phe Glu Met Gly Val Val Pro Ser His Ile Ser Ser
1265 1270 1275
Leu Ile Asp Met Gly Gln Gly Ile Leu His Asn Ala Ser Asp Phe
1280 1285 1290
Tyr Gly Leu Ile Ser Glu Arg Phe Ile Asn Tyr Cys Ile Gly Val
1295 1300 1305
Ile Phe Gly Glu Arg Pro Glu Ala Tyr Thr Ser Ser Asp Asp Gln
1310 1315 1320
Ile Thr Leu Phe Asp Lys Arg Leu Ser Asp Leu Val Asp Ser Asp
1325 1330 1335
Pro Glu Glu Val Leu Val Leu Leu Glu Phe His Ser His Leu Ser
1340 1345 1350
Gly Leu Leu Asn Lys Phe Ile Ser Pro Lys Ser Val Val Gly Arg
1355 1360 1365
Phe Ala Ala Glu Phe Lys Ser Arg Phe Tyr Val Trp Gly Glu Glu
1370 1375 1380
Val Pro Leu Leu Thr Lys Phe Val Ser Ala Ala Leu His Asn Val
1385 1390 1395
Lys Cys Lys Glu Pro His Gln Leu Cys Glu Thr Ile Asp Thr Ile
1400 1405 1410
Ala Asp Gln Ala Ile Ala Asn Gly Val Pro Val Phe Leu Val Asn
1415 1420 1425
Cys Ile Gln Arg Arg Thr Leu Asp Leu Leu Lys Tyr Ala Asn Phe
1430 1435 1440
Pro Leu Asp Pro Phe Leu Leu Asn Thr His Thr Asp Val Lys Asp
1445 1450 1455
Trp Leu Asp Gly Ser Arg Gly Tyr Arg Ile Gln Arg Leu Ile Glu
1460 1465 1470
Glu Leu Cys Pro Ser Glu Thr Lys Ile Met Arg Lys Leu Val Arg
1475 1480 1485
Arg Leu His His Lys Leu Lys Asn Gly Glu Cys Asn Glu Glu Phe
1490 1495 1500
Phe Leu Asp Leu Phe Asn Arg Glu Lys Glu Glu Ala Ile Leu Gln
1505 1510 1515
Leu Gly Glu Ile Leu Gly Leu Glu Asp Asp Leu Asn Glu Leu Ala
1520 1525 1530
Ser Ile Asn Trp Leu Asn Leu Asn Glu Met Phe Pro Leu Arg Met
1535 1540 1545
Val Leu Arg Gln Lys Val Val Tyr Pro Ser Val Met Thr Phe Gln
1550 1555 1560
Glu Glu Lys Ile Pro Ser Leu Ile Lys Thr Leu Gln Asn Lys Leu
1565 1570 1575
Cys Ser Lys Phe Thr Arg Gly Ala Gln Lys Leu Leu Ser Glu Ala
1580 1585 1590
Ile Asn Lys Ser Ala Phe Gln Ser Cys Val Ser Ser Gly Phe Ile
1595 1600 1605
Gly Leu Cys Lys Thr Leu Gly Ser Arg Cys Val Arg Asn Lys Asn
1610 1615 1620
Arg Glu Asn Met Tyr Ile Arg Lys Val Leu Glu Asp Leu Thr Met
1625 1630 1635
Asp Glu His Val Thr Arg Val His Lys Gln Asp Gly Val Met Leu
1640 1645 1650
Tyr Ile Cys Asp Lys Gln Arg His Pro Glu Ala His Arg Asp His
1655 1660 1665
Ile Asn Leu Leu Arg Pro Leu Leu Trp Asp Tyr Ile Cys Ile Ser
1670 1675 1680
Leu Ser Asn Ser Phe Glu Leu Gly Val Trp Val Leu Ala Glu Pro
1685 1690 1695
Val Lys Gly Lys Asn Glu Ser Asn Ser Ala Val Arg His Leu Asn
1700 1705 1710
Pro Cys Asp Tyr Val Ala Arg Lys Pro Glu Ser Ser Arg Leu Leu
1715 1720 1725
Glu Asp Lys Val Ser Leu Asn His Val Ile Gln Ser Val Arg Arg
1730 1735 1740
Leu Tyr Pro Lys Ile Phe Glu Asp Gln Leu Leu Pro Phe Met Ser
1745 1750 1755
Asp Val Ser Ser Lys Asn Met Arg Trp Ser Pro Arg Ile Lys Phe
1760 1765 1770
Leu Asp Leu Cys Val Leu Ile Asp Ile Asn Ser Glu Ser Leu Ser
1775 1780 1785
Leu Ile Ser His Val Val Lys Trp Lys Arg Asp Glu His Tyr Thr
1790 1795 1800
Val Leu Phe Ser Asp Leu Val Asn Ser His Gln Arg Ser Asp Ser
1805 1810 1815
Ser Leu Val Asp Glu Phe Val Val Ser Thr Arg Asp Val Cys Lys
1820 1825 1830
Asn Phe Leu Lys Gln Val Tyr Phe Glu Ser Phe Val Arg Glu Phe
1835 1840 1845
Val Ala Thr Ala Arg Thr Leu Gly Asn Phe Ser Trp Phe Pro His
1850 1855 1860
Lys Asp Met Met Pro Ser Glu Asp Gly Ala Glu Ala Leu Gly Pro
1865 1870 1875
Phe Gln Ser Phe Ile Leu Lys Val Val Asn Lys Lys Ile Glu Arg
1880 1885 1890
Pro Met Phe Arg Asn Asp Leu Gln Phe Gly Phe Gly Trp Phe Ser
1895 1900 1905
Tyr Arg Val Gly Asp Val Val Cys Asn Ala Ala Met Leu Ile Lys
1910 1915 1920
Gln Gly Leu Thr Asp Pro Lys Ala Phe Lys Ser Leu Arg Asp Leu
1925 1930 1935
Trp Asp Tyr Met Leu Ser Ser Thr Glu Gly Ile Leu Glu Phe Ser
1940 1945 1950
Ile Thr Val Asp Phe Thr His Asn Gln Asn Asn Thr Asp Cys Leu
1955 1960 1965
Arg Lys Phe Ser Leu Ile Phe Val Val Lys Cys Gln Leu Gln Ser
1970 1975 1980
Pro Gly Val Ala Asp Tyr Leu Ser Cys Ser His Ser Phe Lys Gly
1985 1990 1995
Glu Val Asp Arg Arg Leu Leu Asp Glu Cys Leu Asn Leu Leu Arg
2000 2005 2010
Thr Asp Pro Ile Phe Lys Ala Asn Asp Gly Val Phe Asp Ile Arg
2015 2020 2025
Ser Glu Glu Phe Glu Asp Tyr Met Glu Asp Pro Leu Thr Leu Gly
2030 2035 2040
Asp Ser Leu Glu Leu Glu Leu Ile Gly Ser Arg Arg Ile Leu Asn
2045 2050 2055
Glu Ile Lys Ser Thr Asp Phe Glu Arg Ile Gly Pro Glu Trp Glu
2060 2065 2070
Pro Val Pro Leu Thr Ile Arg Lys Gly Ala Leu Phe Glu Gly Arg
2075 2080 2085
Asn Phe Val Gln Asn Ile Ser Val Lys Leu Glu Thr Lys Asp Met
2090 2095 2100
Arg Val Phe Leu Ala Glu Leu Glu Gly Cys Gly Lys Ile Gly Asp
2105 2110 2115
Val Leu Gly Ser Leu Leu Leu His Arg Phe Arg Thr Gly Glu His
2120 2125 2130
Leu Met Glu Ser Glu Ile Ser Thr Val Leu Gln Glu Leu Cys Met
2135 2140 2145
Asp Arg Ser Val Met Leu Thr Pro Leu Ser Phe Val Pro Asp Trp
2150 2155 2160
Phe Thr Phe Arg Asp Cys Arg Leu Cys Phe Ser Lys Ser Lys Asn
2165 2170 2175
Thr Val Met Tyr Glu Thr Thr Gly Gly Arg Phe Arg Leu Lys Gly
2180 2185 2190
Lys Ser Cys Asp Asp Trp Leu Ala Glu Arg Val Ala Glu Glu Ile
2195 2200 2205
Asp
<210> 6
<211> 6630
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒
<220>
<221> MISC_FEATURE
<223> 淋巴细胞性脉络丛脑膜炎病毒突变体L-蛋白;ssrna
双义-链病毒;沙粒病毒科;沙粒病毒;旧大陆沙粒病毒
<400> 6
atggatgaaa ctattgcaga tttgagagag ttgtgtctaa attacataga acaggacgag 60
aggctgtcaa ggcaaaaact caacttcctg ggacaaagag aacccagaat ggtgctaatt 120
gagggactca aattgttatc acgctgtata gagatagaca gtgcagacaa aagtggttgc 180
atacacaacc acgatgacaa atctgttgaa acaatcctaa tagactctgg gattgtgtgt 240
ccaggactgc cactcatcat ccctgatggt tataagttga ttgacaattc ccttattctt 300
cttgaatgtt ttgttagaag cacaccagct agttttgaaa agaagttcat tgaggacacc 360
aacaaactag catgcatcaa agaagatctt gctgttgcag gcatcacact ggttccaata 420
gtggatggtc gttgtgatta tgataacagt ttcatgccag aatgggtgaa ttttaagttc 480
agagacctcc tatttaaact cctggagtat tctagtcaag atgagaaagt ttttgaggag 540
tctgaatact tcaggctctg tgagtctctt aagaccactg ttgacaaacg ttccggcatg 600
gactcaatga aaattttgaa agacgcaaga tcatttcata acgatgagat tatgaaaatg 660
tgccacgatg gtgtcaaccc caacatgagt tgcgatgatg tggtctttgg cataaattcc 720
ttttttggca ggtttaggag ggacctgtta aatgggaaac tcaaaaggaa tttccaaaag 780
gtcagccctg ggggcttaat caaggaattc tctgaacttt atgaaaccct tactgataat 840
gatgacatat taatgttgag caaagaggca gttgaatcct gccccttaat gaggttcatt 900
acagcagaga cccatgggca tgagagagga agcgatgcta acactgagta tgaaaggcta 960
ctctctatgt tgaacaaggt gaaaagttta aaattattaa acactagaag gagacagctg 1020
ctgaacttag atgtcttatg tctttcttca cttattaagc agtcaatttc caaagggttg 1080
gaaaatgata aacattgggt tggttgctgc tacagtagtg tgaatgatag gcttgtgagc 1140
cttcaaagta ccaaagaaga attcatgaga cttttgaaga acagaagaaa atcaagagtg 1200
cacaaaaagg catctcttga tgagcttttt agggtatcca taaatgagtt catagcaaaa 1260
atccagaaat gcctatcaac agtgggactt agttttgagc attacggact atcagaatgc 1320
ctcgtgcaag aatgccatat accatttgct gaatttgaga actttatgag agccgggact 1380
catcctgtaa tgcattacac aaaatttgaa gattacactt tccagcctaa catagagcaa 1440
ttgaggggtt tacagagttt gagaaaactg tcatctgttt gtttggctct aacaaacagc 1500
atgaaaacaa gctcagttgc aaggttgaga cagaaccaac tggggtctgt gagatatcaa 1560
gtggtggagt gcaaagaggt gttttgccag ataataaaac tggattccga agagtatcat 1620
ctactatatc agaaaactgg agaatcatcg aggtgttatt ccatacaagg tccggatggt 1680
cacttgattt ccttttacgc agatccaaaa aggttctttt taccaatttt ttcagatgag 1740
gtgttgcaca acatgataga cacaatgatt tcatggatta ggtcatgccc tgacttaaaa 1800
gattctctta ttgacattga gactgcacta aggacattga tcctactgat gctcaccaac 1860
ccaacaaaga gaaatcaaaa gcaggttcaa aatattaggt atttagtgat ggccatcgtc 1920
tcagactttt catcgacctc attaatggat aagttgaagg aggatctaat cacacctgcc 1980
gagaaagtgg tgtacaggct gcttcggttt ttgattagga caatttttgg tactggtgaa 2040
aaggtgttat tgagtgcaaa attcaagttt atgttgaatg tgtcatacct gtgtcatttg 2100
atcacaaagg agacccctga tagattgaca gatcagataa aatgttttga aaagttcttt 2160
gagcccaaga gtgagtttgg tttctttgtc aaccctaagg aaacaatcac acccgaagag 2220
gaatgtgttt tttatgaaca aatgaagaag ttcaccggta aagatattga ttgtcagcat 2280
tcaacccctg gtgttaattt agagatcttt agcatgatgg tatcttcatt caacaatggc 2340
accttaattc taaaagggga gaaaaggctc aacaatctgg accccatgac caactctgga 2400
tgtgcgacag cattagatct cgcaagcaac aaaagtgtgg ttgtcaataa acatctgaat 2460
ggagaacggc ttttggagta tgattttaac aaattgcttg ttagtgctgt gagccaaatt 2520
acagagggct tcatgaggaa acaaaagtat aagctgagac actcagatta cgaatataag 2580
gtctcaaagc ttgtctctag attagtcatc ggttccagga aaacagaagt agacaaattg 2640
gaagatgatc cggtagatgt gtgtttcgag ggggaggagg agacaagttt tttcaggagt 2700
ttagaagata aggtcagctc cacaataaca cggtataata gaggcactag gcttaatgaa 2760
gggcaagggg agggagaatt caagaacaca aaaggactac accaccttca gattattttg 2820
tcaggtaaaa gagcttatct gaggaaagtc attttatcag aaatttcatt tcatctagta 2880
gaggactttg atccatcctg tctcaccaat gacgacatga ggtttatttg tgaggctgtt 2940
gaaggttcaa cagaactgtc accattgtat tttacatcag ctgtcaaaga acaatgtggt 3000
ctggatgaga tggcaagaaa cctctgtaga aagttcttct cagagggtga ttggttctca 3060
tgtatgaaga tgatcttgtt acagatgaat gcaaatgcgt attcagggaa gtacagacac 3120
atgcagaggc agagcttaaa ttttaaattt gactgggaca aattggaaga agatgtaaga 3180
attagtgaaa gggaaagcaa ttctgaatct ctaagtaagg ccctttcatt gacaaaatgc 3240
atgagtgctg ctctaaagaa tctgtgtttt tactcagaag aatcaccaac atcatacact 3300
tcagttggcc ctgactctgg gagactaaaa tttgcattgt catacaaaga gcaggttggg 3360
ggaaatagag agctttacat tggggatttg aggacaaaaa tgttcacaag attggtagaa 3420
gattattttg aatccttttc tagtttcttt tcaggatctt gtttaaacaa tgataaagag 3480
tttgaaaatg caatcttgtc aatgactatc aatgtgagag aagggttgtt aaactacagc 3540
atggatcaca gcaaatgggg accaatgatg tgcccattcc tattcttaat gcttctccaa 3600
aatctcaaac tgggtgatga tcagtacgtg cgttctggaa aagatcatgt tagcaccttg 3660
ttgacttggc atatgcataa acttgttgaa gtccctttcc ctgttgtgaa tgcaatgatg 3720
aaatcatatg ttaaatcaaa actcaagctt ctcaaagggt caggaacgac tgttacggag 3780
agaatcttta gagagtattt tgaaatgggg gtggtgccat ctcacatatc tagtctcatt 3840
gacatgggac aggggatcct acacaatgct tctgattttt acggtttaat tagtgaaagg 3900
tttatcaatt attgtattgg tgtcattttt ggagagaggc cagaagccta tacatcaagt 3960
gatgatcaga tcactttatt tgacaagaga ttgagtgact tagttgatag tgacccagaa 4020
gaagtccttg tcttgctgga attccactct cacttaagtg gtttgttgaa caagttcatc 4080
agtccaaaaa gtgtggttgg gcggtttgca gcggaattca aatccagatt ttatgtgtgg 4140
ggggaggagg tccctctcct cacgaaattt gtgtctgcgg cactacacaa tgttaagtgt 4200
aaagaaccgc atcaactttg tgagacaata gatacgattg ctgatcaagc tatagcaaat 4260
ggagttccag tttttttagt aaactgtatc cagaggagga cactggatct cttgaaatat 4320
gctaatttcc ctttagatcc attcttgtta aacactcaca ctgatgtaaa ggattggtta 4380
gatggttcta gaggttatag aatccaaaga ctcattgaag aattgtgtcc cagtgaaaca 4440
aagatcatga gaaaacttgt aagaagacta catcacaaac tcaagaacgg tgaatgtaac 4500
gaggaatttt ttctagacct cttcaacagg gaaaaggaag aggccatcct tcaattggga 4560
gagattcttg gtcttgagga tgatcttaat gagttggcaa gcatcaattg gttgaatctg 4620
aatgaaatgt tcccattgag gatggttctg agacaaaaag tggtttaccc atcagtaatg 4680
acctttcaag aggaaaagat cccctcattg attaaaacac tccaaaataa gctttgtagt 4740
aagttcacaa gaggtgcaca gaagctgttg tcagaggcaa tcaacaaatc agcttttcag 4800
agttgtgtct catccggctt tataggtctc tgtaagactt taggaagtag gtgtgtgaga 4860
aataaaaaca gggaaaatat gtatatcaga aaggtgcttg aagatctgac catggatgaa 4920
catgtcacaa gggttcacaa acaagatggt gtgatgttgt acatttgcga caagcagaga 4980
cacccagagg ctcaccgtga ccacatcaac cttttgaggc cccttctctg ggactacatt 5040
tgcatctcat tgagcaactc ttttgagctg ggtgtttggg ttttagcaga acctgtgaaa 5100
ggaaagaacg agagtaattc ggctgttagg cacttaaatc catgtgatta tgtagcaaga 5160
aaacctgaga gttcgagact actagaggat aaagtgagtt tgaatcatgt aattcaatct 5220
gtgaggcgac tgtaccccaa aatctttgag gatcagttgc tcccattcat gtctgatgtg 5280
agctcaaaaa atatgagatg gagtcccagg attaaattcc ttgacctttg tgtgctgatt 5340
gacatcaact cagagtcttt gtcactcatt tctcatgttg tcaaatggaa gagggacgaa 5400
cattacactg tgctgttttc tgatctcgtc aactctcacc aacggtcaga ctcaagttta 5460
gttgatgaat ttgttgtcag cacaagggat gtctgcaaga actttttgaa gcaagtgtat 5520
ttcgaatcat ttgtacgaga gtttgttgca acagctagga ccttaggtaa cttttcatgg 5580
ttcccccata aggacatgat gccatctgaa gatggcgctg aagcactggg acccttccaa 5640
tcatttattt tgaaagtggt gaacaagaaa atagagaggc ccatgtttag gaatgacttg 5700
cagtttggtt ttggttggtt ctcttatcgt gtgggggatg ttgtgtgtaa tgccgctatg 5760
ttaattaagc agggtttgac agatccaaaa gcatttaaat ctttaagaga tttgtgggat 5820
tacatgctca gcagcacaga ggggatattg gagttctcaa tcacagtgga tttcacacac 5880
aaccagaaca acactgactg cttgaggaaa ttttcattga tctttgtggt taaatgccaa 5940
ttacagagtc caggtgtagc tgattactta tcgtgctctc attccttcaa aggtgaggtt 6000
gacaggagat tattagatga gtgtctcaat ctgttgagga cagaccccat ctttaaagcg 6060
aatgatggag tctttgacat taggtctgaa gagtttgaag attacatgga agaccctttg 6120
acacttggtg attcactaga acttgaacta ataggttcta gaaggattct gaatgagatc 6180
aaatctactg actttgagag gatagggcct gagtgggaac ctgtgcctct gaccataagg 6240
aagggtgccc tctttgaggg gaggaacttt gttcagaata tctctgtgaa attggagaca 6300
aaggacatga gggtctttct ggcagagctc gagggctgtg gaaaaattgg tgatgtcctc 6360
ggcagcctcc tcctgcaccg attcagaact ggtgagcact tgatggagtc agaaataagt 6420
acagttcttc aggagctctg catggacaga tccgtcatgc tgacaccatt atcttttgtg 6480
ccagattggt tcaccttcag agattgtagg ctctgcttca gcaagtcaaa gaacactgta 6540
atgtatgaga caactggggg caggttcaga ctcaagggga aatcctgtga cgattggctg 6600
gcggagcggg tggccgagga gatcgactag 6630
<210> 7
<211> 2209
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒
<220>
<221> MISC_FEATURE
<223> 淋巴细胞性脉络丛脑膜炎病毒野生型L-蛋白;ssrna
双义-链病毒;沙粒病毒科;沙粒病毒;旧大陆沙粒病毒
<400> 7
Met Asp Glu Thr Ile Ala Asp Leu Arg Glu Leu Cys Leu Asn Tyr Ile
1 5 10 15
Glu Gln Asp Glu Arg Leu Ser Arg Gln Lys Leu Asn Phe Leu Gly Gln
20 25 30
Arg Glu Pro Arg Met Val Leu Ile Glu Gly Leu Lys Leu Leu Ser Arg
35 40 45
Cys Ile Glu Ile Asp Ser Ala Asp Lys Ser Gly Cys Ile His Asn His
50 55 60
Asp Asp Lys Ser Val Glu Thr Ile Leu Ile Asp Ser Gly Ile Val Cys
65 70 75 80
Pro Gly Leu Pro Leu Ile Ile Pro Asp Gly Tyr Lys Leu Ile Asp Asn
85 90 95
Ser Leu Ile Leu Leu Glu Cys Phe Val Arg Ser Thr Pro Ala Ser Phe
100 105 110
Glu Lys Lys Phe Ile Glu Asp Thr Asn Lys Leu Ala Cys Ile Lys Glu
115 120 125
Asp Leu Ala Val Ala Gly Ile Thr Leu Val Pro Ile Val Asp Gly Arg
130 135 140
Cys Asp Tyr Asp Asn Ser Phe Met Pro Glu Trp Val Asn Phe Lys Phe
145 150 155 160
Arg Asp Leu Leu Phe Lys Leu Leu Glu Tyr Ser Ser Gln Asp Glu Lys
165 170 175
Val Phe Glu Glu Ser Glu Tyr Phe Arg Leu Cys Glu Ser Leu Lys Thr
180 185 190
Thr Val Asp Lys Arg Ser Gly Met Asp Ser Met Lys Ile Leu Lys Asp
195 200 205
Ala Arg Ser Phe His Asn Asp Glu Ile Met Lys Met Cys His Asp Gly
210 215 220
Val Asn Pro Asn Met Ser Cys Asp Asp Val Val Phe Gly Ile Asn Ser
225 230 235 240
Phe Phe Gly Arg Phe Arg Arg Asp Leu Leu Asn Gly Lys Leu Lys Arg
245 250 255
Asn Phe Gln Lys Val Ser Pro Gly Gly Leu Ile Lys Glu Phe Ser Glu
260 265 270
Leu Tyr Glu Thr Leu Thr Asp Asn Asp Asp Ile Leu Met Leu Ser Lys
275 280 285
Glu Ala Val Glu Ser Cys Pro Leu Met Arg Phe Ile Thr Ala Glu Thr
290 295 300
His Gly His Glu Arg Gly Ser Asp Ala Asn Thr Glu Tyr Glu Arg Leu
305 310 315 320
Leu Ser Met Leu Asn Lys Val Lys Ser Leu Lys Leu Leu Asn Thr Arg
325 330 335
Arg Arg Gln Leu Leu Asn Leu Asp Val Leu Cys Leu Ser Ser Leu Ile
340 345 350
Lys Gln Ser Ile Ser Lys Gly Leu Glu Asn Asp Lys His Trp Val Gly
355 360 365
Cys Cys Tyr Ser Ser Val Asn Asp Arg Leu Val Ser Leu Gln Ser Thr
370 375 380
Lys Glu Glu Phe Met Arg Leu Leu Lys Asn Arg Arg Lys Ser Arg Val
385 390 395 400
His Lys Lys Ala Ser Leu Asp Glu Leu Phe Arg Val Ser Ile Asn Glu
405 410 415
Phe Ile Ala Lys Ile Gln Lys Cys Leu Ser Thr Val Gly Leu Ser Phe
420 425 430
Glu His Tyr Gly Leu Ser Glu Cys Leu Val Gln Glu Cys His Ile Pro
435 440 445
Phe Ala Glu Phe Glu Asn Phe Met Arg Ala Gly Thr His Pro Val Met
450 455 460
His Tyr Thr Lys Phe Glu Asp Tyr Thr Phe Gln Pro Asn Ile Glu Gln
465 470 475 480
Leu Arg Gly Leu Gln Ser Leu Arg Lys Leu Ser Ser Val Cys Leu Ala
485 490 495
Leu Thr Asn Ser Met Lys Thr Ser Ser Val Ala Arg Leu Arg Gln Asn
500 505 510
Gln Leu Gly Ser Val Arg Tyr Gln Val Val Glu Cys Lys Glu Val Phe
515 520 525
Cys Gln Ile Ile Lys Leu Asp Ser Glu Glu Tyr His Leu Leu Tyr Gln
530 535 540
Lys Thr Gly Glu Ser Ser Arg Cys Tyr Ser Ile Gln Gly Pro Asp Gly
545 550 555 560
His Leu Ile Ser Phe Tyr Ala Asp Pro Lys Arg Phe Phe Leu Pro Ile
565 570 575
Phe Ser Asp Glu Val Leu His Asn Met Ile Asp Thr Met Ile Ser Trp
580 585 590
Ile Arg Ser Cys Pro Asp Leu Lys Asp Ser Leu Ile Asp Ile Glu Thr
595 600 605
Ala Leu Arg Thr Leu Ile Leu Leu Met Leu Thr Asn Pro Thr Lys Arg
610 615 620
Asn Gln Lys Gln Val Gln Asn Ile Arg Tyr Leu Val Met Ala Ile Val
625 630 635 640
Ser Asp Phe Ser Ser Thr Ser Leu Met Asp Lys Leu Lys Glu Asp Leu
645 650 655
Ile Thr Pro Ala Glu Lys Val Val Tyr Arg Leu Leu Arg Phe Leu Ile
660 665 670
Arg Thr Ile Phe Gly Thr Gly Glu Lys Val Leu Leu Ser Ala Lys Phe
675 680 685
Lys Phe Met Leu Asn Val Ser Tyr Leu Cys His Leu Ile Thr Lys Glu
690 695 700
Thr Pro Asp Arg Leu Thr Asp Gln Ile Lys Cys Phe Glu Lys Phe Phe
705 710 715 720
Glu Pro Lys Ser Glu Phe Gly Phe Phe Val Asn Pro Lys Glu Thr Ile
725 730 735
Thr Pro Glu Glu Glu Cys Val Phe Tyr Glu Gln Met Lys Lys Phe Thr
740 745 750
Gly Lys Asp Ile Asp Cys Gln His Ser Thr Pro Gly Val Asn Leu Glu
755 760 765
Ile Phe Ser Met Met Val Ser Ser Phe Asn Asn Gly Thr Leu Ile Leu
770 775 780
Lys Gly Glu Lys Arg Leu Asn Asn Leu Asp Pro Met Thr Asn Ser Gly
785 790 795 800
Cys Ala Thr Ala Leu Asp Leu Ala Ser Asn Lys Ser Val Val Val Asn
805 810 815
Lys His Leu Asn Gly Glu Arg Leu Leu Glu Tyr Asp Phe Asn Lys Leu
820 825 830
Leu Val Ser Ala Val Ser Gln Ile Thr Glu Gly Phe Met Arg Lys Gln
835 840 845
Lys Tyr Lys Leu Arg His Ser Asp Tyr Glu Tyr Lys Val Ser Lys Leu
850 855 860
Val Ser Arg Leu Val Ile Gly Ser Arg Lys Thr Glu Val Asp Lys Leu
865 870 875 880
Glu Asp Asp Pro Val Asp Val Cys Phe Glu Gly Glu Glu Glu Thr Ser
885 890 895
Phe Phe Arg Ser Leu Glu Asp Lys Val Ser Ser Thr Ile Thr Arg Tyr
900 905 910
Asn Arg Gly Thr Arg Leu Asn Glu Gly Gln Gly Glu Gly Glu Phe Lys
915 920 925
Asn Thr Lys Gly Leu His His Leu Gln Ile Ile Leu Ser Gly Lys Arg
930 935 940
Ala Tyr Leu Arg Lys Val Ile Leu Ser Glu Ile Ser Phe His Leu Val
945 950 955 960
Glu Asp Phe Asp Pro Ser Cys Leu Thr Asn Asp Asp Met Arg Phe Ile
965 970 975
Cys Glu Ala Val Glu Gly Ser Thr Glu Leu Ser Pro Leu Tyr Phe Thr
980 985 990
Ser Ala Val Lys Glu Gln Cys Gly Leu Asp Glu Met Ala Arg Asn Leu
995 1000 1005
Cys Arg Lys Phe Phe Ser Glu Gly Asp Trp Phe Ser Cys Met Lys
1010 1015 1020
Met Ile Leu Leu Gln Met Asn Ala Asn Ala Tyr Ser Gly Lys Tyr
1025 1030 1035
Arg His Met Gln Arg Gln Ser Leu Asn Phe Lys Phe Asp Trp Asp
1040 1045 1050
Lys Leu Glu Glu Asp Val Arg Ile Ser Glu Arg Glu Ser Asn Ser
1055 1060 1065
Glu Ser Leu Ser Lys Ala Leu Ser Leu Thr Lys Cys Met Ser Ala
1070 1075 1080
Ala Leu Lys Asn Leu Cys Phe Tyr Ser Glu Glu Ser Pro Thr Ser
1085 1090 1095
Tyr Thr Ser Val Gly Pro Asp Ser Gly Arg Leu Lys Phe Ala Leu
1100 1105 1110
Ser Tyr Lys Glu Gln Val Gly Gly Asn Arg Glu Leu Tyr Ile Gly
1115 1120 1125
Asp Leu Arg Thr Lys Met Phe Thr Arg Leu Val Glu Asp Tyr Phe
1130 1135 1140
Glu Ser Phe Ser Ser Phe Phe Ser Gly Ser Cys Leu Asn Asn Asp
1145 1150 1155
Lys Glu Phe Glu Asn Ala Ile Leu Ser Met Thr Ile Asn Val Arg
1160 1165 1170
Glu Gly Leu Leu Asn Tyr Ser Met Asp His Ser Lys Trp Gly Pro
1175 1180 1185
Met Met Cys Pro Phe Leu Phe Leu Met Leu Leu Gln Asn Leu Lys
1190 1195 1200
Leu Gly Asp Asp Gln Tyr Val Arg Ser Gly Lys Asp His Val Ser
1205 1210 1215
Thr Leu Leu Thr Trp His Met His Lys Leu Val Glu Val Pro Phe
1220 1225 1230
Pro Val Val Asn Ala Met Met Lys Ser Tyr Val Lys Ser Lys Leu
1235 1240 1245
Lys Leu Leu Lys Gly Ser Gly Thr Thr Val Thr Glu Arg Ile Phe
1250 1255 1260
Arg Glu Tyr Phe Glu Met Gly Val Val Pro Ser His Ile Ser Ser
1265 1270 1275
Leu Ile Asp Met Gly Gln Gly Ile Leu His Asn Ala Ser Asp Phe
1280 1285 1290
Tyr Gly Leu Ile Ser Glu Arg Phe Ile Asn Tyr Cys Ile Gly Val
1295 1300 1305
Ile Phe Gly Glu Arg Pro Glu Ala Tyr Thr Ser Ser Asp Asp Gln
1310 1315 1320
Ile Thr Leu Phe Asp Lys Arg Leu Ser Asp Leu Val Asp Ser Asp
1325 1330 1335
Pro Glu Glu Val Leu Val Leu Leu Glu Phe His Ser His Leu Ser
1340 1345 1350
Gly Leu Leu Asn Lys Phe Ile Ser Pro Lys Ser Val Val Gly Arg
1355 1360 1365
Phe Ala Ala Glu Phe Lys Ser Arg Phe Tyr Val Trp Gly Glu Glu
1370 1375 1380
Val Pro Leu Leu Thr Lys Phe Val Ser Ala Ala Leu His Asn Val
1385 1390 1395
Lys Cys Lys Glu Pro His Gln Leu Cys Glu Thr Ile Asp Thr Ile
1400 1405 1410
Ala Asp Gln Ala Ile Ala Asn Gly Val Pro Val Phe Leu Val Asn
1415 1420 1425
Cys Ile Gln Arg Arg Thr Leu Asp Leu Leu Lys Tyr Ala Asn Phe
1430 1435 1440
Pro Leu Asp Pro Phe Leu Leu Asn Thr His Thr Asp Val Lys Asp
1445 1450 1455
Trp Leu Asp Gly Ser Arg Gly Tyr Arg Ile Gln Arg Leu Ile Glu
1460 1465 1470
Glu Leu Cys Pro Ser Glu Thr Lys Ile Met Arg Lys Leu Val Arg
1475 1480 1485
Arg Leu His His Lys Leu Lys Asn Gly Glu Cys Asn Glu Glu Phe
1490 1495 1500
Phe Leu Asp Leu Phe Asn Arg Glu Lys Lys Glu Ala Ile Leu Gln
1505 1510 1515
Leu Gly Glu Ile Leu Gly Leu Glu Asp Asp Leu Asn Glu Leu Ala
1520 1525 1530
Ser Ile Asn Trp Leu Asn Leu Asn Glu Met Phe Pro Leu Arg Met
1535 1540 1545
Val Leu Arg Gln Lys Val Val Tyr Pro Ser Val Met Thr Phe Gln
1550 1555 1560
Glu Glu Lys Ile Pro Ser Leu Ile Lys Thr Leu Gln Asn Lys Leu
1565 1570 1575
Cys Ser Lys Phe Thr Arg Gly Ala Gln Lys Leu Leu Ser Glu Ala
1580 1585 1590
Ile Asn Lys Ser Ala Phe Gln Ser Cys Val Ser Ser Gly Phe Ile
1595 1600 1605
Gly Leu Cys Lys Thr Leu Gly Ser Arg Cys Val Arg Asn Lys Asn
1610 1615 1620
Arg Glu Asn Met Tyr Ile Arg Lys Val Leu Glu Asp Leu Thr Met
1625 1630 1635
Asp Glu His Val Thr Arg Val His Lys Gln Asp Gly Val Met Leu
1640 1645 1650
Tyr Ile Cys Asp Lys Gln Arg His Pro Glu Ala His Arg Asp His
1655 1660 1665
Ile Asn Leu Leu Arg Pro Leu Leu Trp Asp Tyr Ile Cys Ile Ser
1670 1675 1680
Leu Ser Asn Ser Phe Glu Leu Gly Val Trp Val Leu Ala Glu Pro
1685 1690 1695
Val Lys Gly Lys Asn Glu Ser Asn Ser Ala Val Arg His Leu Asn
1700 1705 1710
Pro Cys Asp Tyr Val Ala Arg Lys Pro Glu Ser Ser Arg Leu Leu
1715 1720 1725
Glu Asp Lys Val Ser Leu Asn His Val Ile Gln Ser Val Arg Arg
1730 1735 1740
Leu Tyr Pro Lys Ile Phe Glu Asp Gln Leu Leu Pro Phe Met Phe
1745 1750 1755
Asp Val Ser Ser Lys Asn Met Arg Trp Ser Pro Arg Ile Lys Phe
1760 1765 1770
Leu Asp Leu Cys Val Leu Ile Asp Ile Asn Ser Glu Ser Leu Ser
1775 1780 1785
Leu Ile Ser His Val Val Lys Trp Lys Arg Asp Glu His Tyr Thr
1790 1795 1800
Val Leu Phe Ser Asp Leu Val Asn Ser His Gln Arg Ser Asp Ser
1805 1810 1815
Ser Leu Val Asp Glu Phe Val Val Ser Thr Arg Asp Val Cys Lys
1820 1825 1830
Asn Phe Leu Lys Gln Val Tyr Phe Glu Ser Phe Val Arg Glu Phe
1835 1840 1845
Val Ala Thr Ala Arg Thr Leu Gly Asn Phe Ser Trp Phe Pro His
1850 1855 1860
Lys Asp Met Met Pro Ser Glu Asp Gly Ala Glu Ala Leu Gly Pro
1865 1870 1875
Phe Gln Ser Phe Ile Leu Lys Val Val Asn Lys Lys Ile Glu Arg
1880 1885 1890
Pro Met Phe Arg Asn Asp Leu Gln Phe Gly Phe Gly Trp Phe Ser
1895 1900 1905
Tyr Arg Val Gly Asp Val Val Cys Asn Ala Ala Met Leu Ile Lys
1910 1915 1920
Gln Gly Leu Thr Asp Pro Lys Ala Phe Lys Ser Leu Arg Asp Leu
1925 1930 1935
Trp Asp Tyr Met Leu Ser Ser Thr Glu Gly Ile Leu Glu Phe Ser
1940 1945 1950
Ile Thr Val Asp Phe Thr His Asn Gln Asn Asn Thr Asp Cys Leu
1955 1960 1965
Arg Lys Phe Ser Leu Ile Phe Val Val Lys Cys Gln Leu Gln Ser
1970 1975 1980
Pro Gly Val Ala Asp Tyr Leu Ser Cys Ser His Phe Phe Lys Gly
1985 1990 1995
Glu Val Asp Arg Arg Leu Leu Asp Glu Cys Leu Asn Leu Leu Arg
2000 2005 2010
Thr Asp Pro Ile Phe Lys Ala Asn Asp Gly Val Phe Asp Ile Arg
2015 2020 2025
Ser Glu Glu Phe Glu Asp Tyr Met Glu Asp Pro Leu Thr Leu Gly
2030 2035 2040
Asp Ser Leu Glu Leu Glu Leu Ile Gly Ser Arg Arg Ile Leu Asn
2045 2050 2055
Glu Ile Lys Ser Thr Asp Phe Glu Arg Ile Gly Pro Glu Trp Glu
2060 2065 2070
Pro Val Pro Leu Thr Ile Arg Lys Gly Ala Leu Phe Glu Gly Arg
2075 2080 2085
Asn Phe Val Gln Asn Ile Ser Val Lys Leu Glu Thr Lys Asp Met
2090 2095 2100
Arg Val Phe Leu Ala Glu Leu Glu Gly Cys Gly Lys Ile Gly Asp
2105 2110 2115
Val Leu Gly Ser Leu Leu Leu His Arg Phe Arg Thr Gly Glu His
2120 2125 2130
Leu Met Glu Ser Glu Ile Ser Thr Val Leu Gln Glu Leu Cys Met
2135 2140 2145
Asp Arg Ser Val Met Leu Thr Pro Leu Ser Phe Val Pro Asp Trp
2150 2155 2160
Phe Thr Phe Arg Asp Cys Arg Leu Cys Phe Ser Arg Ser Lys Asn
2165 2170 2175
Thr Val Met Tyr Glu Thr Thr Gly Gly Arg Phe Arg Leu Lys Gly
2180 2185 2190
Lys Ser Cys Asp Asp Trp Leu Ala Glu Arg Val Ala Glu Glu Ile
2195 2200 2205
Asp
<210> 8
<211> 6630
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒
<220>
<221> MISC_FEATURE
<223> 淋巴细胞性脉络丛脑膜炎病毒野生型L-蛋白;ssrna
双义-链病毒;沙粒病毒科;沙粒病毒;旧大陆沙粒病毒
<400> 8
atggatgaaa ctattgcaga tttgagagag ttgtgtctaa attacataga acaggacgag 60
aggctgtcaa ggcaaaaact caacttcctg ggacaaagag aacccagaat ggtgctaatt 120
gagggactca aattgttatc acgctgtata gagatagaca gtgcagacaa aagtggttgc 180
atacacaacc acgatgacaa atctgttgaa acaatcctaa tagactctgg gattgtgtgt 240
ccaggactgc cactcatcat ccctgatggt tataagttga ttgacaattc ccttattctt 300
cttgaatgtt ttgttagaag cacaccagct agttttgaaa agaagttcat tgaggacacc 360
aacaaactag catgcatcaa agaagatctt gctgttgcag gcatcacact ggttccaata 420
gtggatggtc gttgtgatta tgataacagt ttcatgccag aatgggtgaa ttttaagttc 480
agagacctcc tatttaaact cctggagtat tctagtcaag atgagaaagt ttttgaggag 540
tctgaatact tcaggctctg tgagtctctt aagaccactg ttgacaaacg ttccggcatg 600
gactcaatga aaattttgaa agacgcaaga tcatttcata acgatgagat tatgaaaatg 660
tgccacgatg gtgtcaaccc caacatgagt tgcgatgatg tggtctttgg cataaattcc 720
ttttttggca ggtttaggag ggacctgtta aatgggaaac tcaaaaggaa tttccaaaag 780
gtcagccctg ggggcttaat caaggaattc tctgaacttt atgaaaccct tactgataat 840
gatgacatat taatgttgag caaagaggca gttgaatcct gccccttaat gaggttcatt 900
acagcagaga cccatgggca tgagagagga agcgatgcta acactgagta tgaaaggcta 960
ctctctatgt tgaacaaggt gaaaagttta aaattattaa acactagaag gagacagctg 1020
ctgaacttag atgtcttatg tctttcttca cttattaagc agtcaatttc caaagggttg 1080
gaaaatgata aacattgggt tggttgttgc tacagtagtg tgaatgatag gcttgtgagc 1140
cttcaaagta ccaaagaaga attcatgaga cttttgaaga acagaagaaa atcaagagtg 1200
cacaaaaagg catctcttga tgagcttttt agggtatcca taaatgagtt catagcaaaa 1260
atccagaaat gcctatcaac agtgggactt agttttgagc attacggact atcagaatgc 1320
ctcgtgcaag aatgccatat accatttgct gaatttgaga actttatgag agccgggact 1380
catcctgtaa tgcattacac aaaatttgaa gattacactt tccagcctaa catagagcaa 1440
ttgaggggtt tacagagttt gagaaaactg tcatctgttt gtttggctct aacaaacagc 1500
atgaaaacaa gctcagttgc aaggttgaga cagaaccaac tggggtctgt gagatatcaa 1560
gtggtggagt gcaaagaggt gttttgccag ataataaaac tggattccga agagtatcat 1620
ctactatatc agaaaactgg agaatcatcg aggtgttatt ccatacaagg tccggatggt 1680
cacttgattt ccttttacgc agatccaaaa aggttctttt taccaatttt ttcagatgag 1740
gtgttgcaca acatgataga cacaatgatt tcatggatta ggtcatgccc tgacttaaaa 1800
gattctctta ttgacattga gactgcacta aggacattga tcctactgat gctcaccaac 1860
ccaacaaaga gaaatcaaaa gcaggttcaa aatattaggt atttagtgat ggccatcgtc 1920
tcagactttt catcgacctc attaatggat aagttgaagg aggatctaat cacacctgcc 1980
gagaaagtgg tgtacaggct gcttcggttt ttgattagga caatttttgg tactggtgaa 2040
aaggtgttat tgagtgcaaa attcaagttt atgttgaatg tgtcatacct gtgtcatttg 2100
atcacaaagg agacccctga tagattgaca gatcagataa aatgttttga aaagttcttt 2160
gagcccaaga gtgagtttgg tttctttgtc aaccctaagg aaacaatcac acccgaagag 2220
gaatgtgttt tttatgaaca aatgaagaag ttcaccggta aagatattga ttgtcagcat 2280
tcaacccctg gtgttaattt agagatcttt agcatgatgg tatcttcatt caacaatggc 2340
accttaattc taaaagggga gaaaaggctc aacaatctgg accccatgac caactctgga 2400
tgtgcgacag cattagatct cgcaagcaac aaaagtgtgg ttgtcaataa acatctgaat 2460
ggagaacggc ttttggagta tgattttaac aaattgcttg ttagtgctgt gagccaaatt 2520
acagagggct tcatgaggaa acaaaagtat aagctgagac actcagatta cgaatataag 2580
gtctcaaagc ttgtctctag attagtcatc ggttccagga aaacagaagt agacaaattg 2640
gaagatgatc cggtagatgt gtgtttcgag ggggaggagg agacaagttt tttcaggagt 2700
ttagaagata aggtcagctc cacaataaca cggtataata gaggcactag gcttaatgaa 2760
gggcaagggg agggagaatt caagaacaca aaaggactac accaccttca gattattttg 2820
tcaggtaaaa gagcttatct gaggaaagtc attttatcag aaatttcatt tcatctagta 2880
gaggactttg atccatcctg tctcaccaat gacgacatga ggtttatttg tgaggctgtt 2940
gaaggttcaa cagaactgtc accattgtat tttacatcag ctgtcaaaga acaatgtggt 3000
ctggatgaga tggcaagaaa cctctgtaga aagttcttct cagagggtga ttggttctca 3060
tgtatgaaga tgatcttgtt acagatgaat gcaaatgcgt attcagggaa gtacagacac 3120
atgcagaggc agagcttaaa ttttaaattt gactgggaca aattggaaga agatgtaaga 3180
attagtgaaa gggaaagcaa ttctgaatct ctaagtaagg ccctttcatt gacaaaatgc 3240
atgagtgctg ctctaaagaa tctgtgtttt tactcagaag aatcaccaac atcatacact 3300
tcagttggcc ctgactctgg gagactaaaa tttgcattgt catacaaaga gcaggttggg 3360
ggaaatagag agctttacat tggggatttg aggacaaaaa tgttcacaag attggtagaa 3420
gattattttg aatccttttc tagtttcttt tcaggatctt gtttaaacaa tgacaaagag 3480
tttgaaaatg caatcttgtc aatgactatc aatgtgagag aagggttgtt aaactacagc 3540
atggatcaca gcaaatgggg accaatgatg tgcccattcc tattcttaat gcttctccaa 3600
aatctcaaac tgggtgatga tcagtacgtg cgttctggaa aagatcatgt tagcaccttg 3660
ttgacttggc atatgcataa acttgttgaa gtccctttcc ctgttgtgaa tgcaatgatg 3720
aaatcatatg ttaaatcaaa actcaagctt ctcaaagggt caggaacgac tgttacggag 3780
agaatcttta gagagtattt tgaaatgggg gtggtgccat ctcacatatc tagtctcatt 3840
gacatgggac aggggatcct acacaatgct tctgattttt acggtttaat tagtgaaagg 3900
tttatcaatt attgtattgg tgtcattttt ggagagaggc cagaagccta tacatcaagt 3960
gatgatcaga tcactttatt tgacaagaga ttgagtgact tagttgatag tgacccagaa 4020
gaagtccttg tcttgctgga attccactct cacttaagtg gtttgttgaa caagttcatc 4080
agtccaaaaa gtgtggttgg gcggtttgca gcggaattca aatccagatt ttatgtgtgg 4140
ggggaggagg tccctctcct cacgaaattt gtgtctgcgg cactacacaa tgttaagtgt 4200
aaagaaccgc atcaactttg tgagacaata gatacgattg ctgatcaagc tatagcaaat 4260
ggagttccag tttttttagt aaactgtatc cagaggagga cactggatct cttgaaatat 4320
gctaatttcc ctttagatcc attcttgtta aacactcaca ctgatgtaaa ggattggtta 4380
gatggttcta gaggttatag aatccaaaga ctcattgaag aattgtgtcc cagtgaaaca 4440
aagatcatga gaaaacttgt aagaagacta catcacaaac tcaagaacgg tgaatgtaac 4500
gaggaatttt ttctagacct cttcaacagg gaaaagaaag aggccatcct tcaattggga 4560
gagattcttg gtcttgagga tgatcttaat gagttggcaa gcatcaattg gttgaatctg 4620
aatgaaatgt tcccattgag gatggttctg agacaaaaag tggtttaccc atcagtaatg 4680
acctttcaag aggaaaagat cccctcattg attaaaacac tccaaaataa gctttgtagt 4740
aagttcacaa gaggtgcaca gaagctgttg tcagaggcaa tcaacaaatc agcttttcag 4800
agttgtgtct catccggctt tataggtctc tgtaagactt taggaagtag gtgtgtgaga 4860
aataaaaaca gggaaaatat gtatatcaga aaggtgcttg aagatctgac catggatgaa 4920
catgtcacaa gggttcacaa acaagatggt gtgatgttgt acatttgcga caagcagaga 4980
cacccagagg ctcaccgtga ccacatcaac cttttgaggc cccttctctg ggactacatt 5040
tgcatctcat tgagcaactc ttttgagctg ggtgtttggg ttttagcaga acctgtgaaa 5100
ggaaagaacg agagtaattc ggctgttagg cacttaaatc catgtgatta tgtagcaaga 5160
aaacctgaga gttcgagact actagaggat aaagtgagtt tgaatcatgt aattcaatct 5220
gtgaggcgac tgtaccccaa aatctttgag gatcagttgc tcccattcat gtctgatgtg 5280
agctcaaaaa atatgagatg gagtcccagg attaaattcc ttgacctttg tgtgctgatt 5340
gacatcaact cagagtcttt gtcactcatt tctcatgttg tcaaatggaa gagggacgaa 5400
cattacactg tgctgttttc tgatctcgtc aactctcacc aacggtcaga ctcaagttta 5460
gttgatgaat ttgttgtcag cacaagggat gtctgcaaga actttttgaa gcaagtgtat 5520
ttcgaatcat ttgtacgaga gtttgttgca acagctagga ccttaggtaa cttttcatgg 5580
ttcccccata aggacatgat gccatctgaa gatggcgctg aagcactggg acccttccaa 5640
tcatttattt tgaaagtggt gaacaagaaa atagagaggc ccatgtttag gaatgacttg 5700
cagtttggtt ttggttggtt ctcttatcgt gtgggggatg ttgtgtgtaa tgccgctatg 5760
ttaattaagc agggtttgac agatccaaaa gcatttaaat ctttaagaga tttgtgggat 5820
tacatgctca gcagcacaga ggggatattg gagttctcaa tcacagtgga tttcacacac 5880
aaccagaaca acactgactg cttgaggaaa ttttcattga tctttgtggt taaatgccaa 5940
ttacagagtc caggtgtagc tgattactta tcgtgctctc atttcttcaa aggtgaggtt 6000
gacaggagat tattagatga gtgtctcaat ctgttgagga cagaccccat ctttaaagcg 6060
aatgatggag tctttgacat taggtctgaa gagtttgaag attacatgga agaccctttg 6120
acacttggtg attcactaga acttgaacta ataggttcta gaaggattct gaatgagatc 6180
aaatctactg actttgagag gatagggcct gagtgggaac ctgtgcctct gaccataagg 6240
aagggtgccc tctttgaggg gaggaacttt gttcagaata tctctgtgaa attggagaca 6300
aaggacatga gggtctttct ggcagagctc gagggctgtg gaaaaattgg tgatgtcctc 6360
ggcagcctcc tcctgcaccg attcagaact ggtgagcact tgatggagtc agaaataagt 6420
acagttcttc aggagctctg catggacaga tccgtcatgc tgacaccatt atcttttgtg 6480
ccagattggt tcaccttcag agattgtagg ctctgcttca gcaggtcaaa gaacactgta 6540
atgtatgaga caactggggg caggttcaga ctcaagggga aatcctgtga cgattggctg 6600
gcggagcggg tggccgagga gatcgactag 6630
<210> 9
<211> 1497
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(株WE)
<400> 9
atgggtcaga ttgtgacaat gtttgaggct ttgcctcaca tcattgatga ggtcatcaac 60
attgtcatta ttgtgctcat tataatcacg agcatcaaag ctgtgtacaa tttcgccacc 120
tgtgggatat tagcactggt cagcttcctt tttttggctg gtaggtcctg tggcatgtac 180
ggccttaatg gtcccgacat ctataaaggg gtttaccagt tcaaatcagt ggagtttgat 240
atgtctcact taaatctgac gatgcccaat gcgtgctcag ccaacaactc tcatcactac 300
atcagtatgg gaagctctgg actggagcta actttcacta acgactccat ccttaatcac 360
aatttttgca acttaacctc cgctttcaac aaaaagactt ttgaccatac actcatgagt 420
atagtctcga gtctgcacct cagtattaga gggaattcca accacaaagc agtgtcttgt 480
gattttaaca atggcatcac cattcaatac aacttgtcat tttcggaccc acagagcgct 540
ataagccagt gtaggacttt cagaggtaga gtcttggaca tgtttagaac tgcctttgga 600
ggaaaataca tgagaagtgg ctggggctgg gcaggttcag atggcaagac cacttggtgc 660
agccaaacaa gctatcagta cctaatcata caaaacagga cttgggaaaa ccactgtaga 720
tatgcaggcc cttttgggat gtctagaatc ctctttgctc aggaaaagac aaagtttctc 780
actaggagac ttgcaggcac attcacctgg accctgtcag actcctcagg agtagaaaat 840
ccaggtggtt attgcctgac caaatggatg atccttgctg cagagctcaa atgttttggg 900
aatacagctg ttgcaaaatg taatgtcaat catgatgaag agttctgtga catgctacga 960
ctaattgatt acaacaaggc cgccctgagt aagttcaagc aagatgtaga gtctgccttg 1020
catgtattca aaacaacagt aaattctctg atttccgatc agctgttgat gaggaatcat 1080
ctaagagatc taatgggggt accatactgt aattactcaa agttctggta tctggaacat 1140
gctaagactg gtgagactag tgtacccaag tgctggcttg tcactaatgg ctcctacttg 1200
aatgagaccc actttagtga tcaaatcgaa caagaagcag ataacatgat cacagagatg 1260
ttgaggaagg actacataaa aagacaaggg agtactcctt tagccttaat ggatcttttg 1320
atgttttcaa catcagcata tctaatcagc atctttctgc atcttgtgaa gataccaaca 1380
catagacaca taaagggcgg ttcatgtcca aagccacacc gcttgaccaa caaggggatc 1440
tgtagttgtg gtgcattcaa ggtgcctggt gtaaaaacta tctggaaaag acgctga 1497
<210> 10
<211> 498
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(株WE)
<400> 10
Met Gly Gln Ile Val Thr Met Phe Glu Ala Leu Pro His Ile Ile Asp
1 5 10 15
Glu Val Ile Asn Ile Val Ile Ile Val Leu Ile Ile Ile Thr Ser Ile
20 25 30
Lys Ala Val Tyr Asn Phe Ala Thr Cys Gly Ile Leu Ala Leu Val Ser
35 40 45
Phe Leu Phe Leu Ala Gly Arg Ser Cys Gly Met Tyr Gly Leu Asn Gly
50 55 60
Pro Asp Ile Tyr Lys Gly Val Tyr Gln Phe Lys Ser Val Glu Phe Asp
65 70 75 80
Met Ser His Leu Asn Leu Thr Met Pro Asn Ala Cys Ser Ala Asn Asn
85 90 95
Ser His His Tyr Ile Ser Met Gly Ser Ser Gly Leu Glu Leu Thr Phe
100 105 110
Thr Asn Asp Ser Ile Leu Asn His Asn Phe Cys Asn Leu Thr Ser Ala
115 120 125
Phe Asn Lys Lys Thr Phe Asp His Thr Leu Met Ser Ile Val Ser Ser
130 135 140
Leu His Leu Ser Ile Arg Gly Asn Ser Asn His Lys Ala Val Ser Cys
145 150 155 160
Asp Phe Asn Asn Gly Ile Thr Ile Gln Tyr Asn Leu Ser Phe Ser Asp
165 170 175
Pro Gln Ser Ala Ile Ser Gln Cys Arg Thr Phe Arg Gly Arg Val Leu
180 185 190
Asp Met Phe Arg Thr Ala Phe Gly Gly Lys Tyr Met Arg Ser Gly Trp
195 200 205
Gly Trp Ala Gly Ser Asp Gly Lys Thr Thr Trp Cys Ser Gln Thr Ser
210 215 220
Tyr Gln Tyr Leu Ile Ile Gln Asn Arg Thr Trp Glu Asn His Cys Arg
225 230 235 240
Tyr Ala Gly Pro Phe Gly Met Ser Arg Ile Leu Phe Ala Gln Glu Lys
245 250 255
Thr Lys Phe Leu Thr Arg Arg Leu Ala Gly Thr Phe Thr Trp Thr Leu
260 265 270
Ser Asp Ser Ser Gly Val Glu Asn Pro Gly Gly Tyr Cys Leu Thr Lys
275 280 285
Trp Met Ile Leu Ala Ala Glu Leu Lys Cys Phe Gly Asn Thr Ala Val
290 295 300
Ala Lys Cys Asn Val Asn His Asp Glu Glu Phe Cys Asp Met Leu Arg
305 310 315 320
Leu Ile Asp Tyr Asn Lys Ala Ala Leu Ser Lys Phe Lys Gln Asp Val
325 330 335
Glu Ser Ala Leu His Val Phe Lys Thr Thr Val Asn Ser Leu Ile Ser
340 345 350
Asp Gln Leu Leu Met Arg Asn His Leu Arg Asp Leu Met Gly Val Pro
355 360 365
Tyr Cys Asn Tyr Ser Lys Phe Trp Tyr Leu Glu His Ala Lys Thr Gly
370 375 380
Glu Thr Ser Val Pro Lys Cys Trp Leu Val Thr Asn Gly Ser Tyr Leu
385 390 395 400
Asn Glu Thr His Phe Ser Asp Gln Ile Glu Gln Glu Ala Asp Asn Met
405 410 415
Ile Thr Glu Met Leu Arg Lys Asp Tyr Ile Lys Arg Gln Gly Ser Thr
420 425 430
Pro Leu Ala Leu Met Asp Leu Leu Met Phe Ser Thr Ser Ala Tyr Leu
435 440 445
Ile Ser Ile Phe Leu His Leu Val Lys Ile Pro Thr His Arg His Ile
450 455 460
Lys Gly Gly Ser Cys Pro Lys Pro His Arg Leu Thr Asn Lys Gly Ile
465 470 475 480
Cys Ser Cys Gly Ala Phe Lys Val Pro Gly Val Lys Thr Ile Trp Lys
485 490 495
Arg Arg
<210> 11
<211> 1677
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(株WE)
<400> 11
atgtctttgt ccaaagaagt caaaagcttt cagtggacac aggcgttgag gagggagttg 60
cagagtttta catcagatgt aaaggctgcc gtcatcaagg acgcaaccag tcttctaaat 120
gggttggact tttctgaagt cagcaacgtt cagaggatca tgagaaagga aaggagggat 180
gataaagact tgcagagact caggagtctt aaccagactg tgcattctct tgttgatctg 240
aagtctacat caaagaaaaa tgttctgaaa gtgggaagac ttagtgcaga ggaattgatg 300
acccttgcag ctgatcttga gaagctgaag gccaaaatta tgagaactga gaggcctcaa 360
gcttctggag tctacatggg aaatttgaca gcacaacaac ttgatcaaag atcccaaata 420
ctgcaaatgg ttgggatgag aagacctcag cagggtgcaa gtggtgtagt aagggtttgg 480
gatgtgaagg actcatcact tctgaacaat cagttcggca caatgccaag cctgacaatg 540
gcttgcatgg caaaacagtc acagacccca ctcaatgatg ttgtgcaggc actcacagac 600
cttggcttac tttacacagt caaatacccg aatctcagtg atcttgaaag gctaaaggat 660
aaacacccag ttctgggggt cattactgaa cagcaatcta gtatcaatat ctctggttat 720
aatttcagtc ttggtgcagc tgtgaaagcg ggggcagctc tgctagatgg agggaacatg 780
ctggaatcta tcttgatcaa accgagcaac agtgaggatc tcctaaaagc agtcctcggg 840
gccaagaaga aactcaacat gtttgtctca gatcaagttg gagatagaaa tccctatgaa 900
aacatccttt ataaagtctg tctttcaggt gaaggatggc catacatagc ctgtagaacg 960
tcagttgtgg ggagagcatg ggagaacaca acaattgatc tcacaaatga aaaacttgtt 1020
gccaactcat ctaggccagt gcctggagca gcaggcccac ctcaggtggg cttgagttac 1080
agtcagacaa tgctgttgaa agacttgatg ggagggattg atcccaatgc tcccacatgg 1140
attgacattg agggcaggtt caatgatcca gtggagatag caatattcca accacaaaat 1200
gggcaattca tacattttta cagggaacct acggaccaga agcaattcaa gcaggactca 1260
aagtattcac acggcatgga tcttgctgat ctcttcaatg cacagcctgg gctgacctca 1320
tcagttatag gtgctctccc acaagggatg gttttgagct gtcaaggttc tgatgacatc 1380
agaaagcttc tggactcaca aaatagaagg gacataaaac tcattgatgt tgagatgacc 1440
aaggaggcct caagagaata tgaagataaa gtgtgggaca aatatggctg gctatgcaaa 1500
atgcacactg gggtagtgag agacaaaaag aagaaagaga tcaccccaca ctgtgcactc 1560
atggactgca tcatttttga gagtgcttcc aaggcaagac tccctgatct aaaaaccgtt 1620
cacaacatcc tgccacatga tttaatcttc agaggaccca atgttgtgac actctaa 1677
<210> 12
<211> 558
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(株WE)
<400> 12
Met Ser Leu Ser Lys Glu Val Lys Ser Phe Gln Trp Thr Gln Ala Leu
1 5 10 15
Arg Arg Glu Leu Gln Ser Phe Thr Ser Asp Val Lys Ala Ala Val Ile
20 25 30
Lys Asp Ala Thr Ser Leu Leu Asn Gly Leu Asp Phe Ser Glu Val Ser
35 40 45
Asn Val Gln Arg Ile Met Arg Lys Glu Arg Arg Asp Asp Lys Asp Leu
50 55 60
Gln Arg Leu Arg Ser Leu Asn Gln Thr Val His Ser Leu Val Asp Leu
65 70 75 80
Lys Ser Thr Ser Lys Lys Asn Val Leu Lys Val Gly Arg Leu Ser Ala
85 90 95
Glu Glu Leu Met Thr Leu Ala Ala Asp Leu Glu Lys Leu Lys Ala Lys
100 105 110
Ile Met Arg Thr Glu Arg Pro Gln Ala Ser Gly Val Tyr Met Gly Asn
115 120 125
Leu Thr Ala Gln Gln Leu Asp Gln Arg Ser Gln Ile Leu Gln Met Val
130 135 140
Gly Met Arg Arg Pro Gln Gln Gly Ala Ser Gly Val Val Arg Val Trp
145 150 155 160
Asp Val Lys Asp Ser Ser Leu Leu Asn Asn Gln Phe Gly Thr Met Pro
165 170 175
Ser Leu Thr Met Ala Cys Met Ala Lys Gln Ser Gln Thr Pro Leu Asn
180 185 190
Asp Val Val Gln Ala Leu Thr Asp Leu Gly Leu Leu Tyr Thr Val Lys
195 200 205
Tyr Pro Asn Leu Ser Asp Leu Glu Arg Leu Lys Asp Lys His Pro Val
210 215 220
Leu Gly Val Ile Thr Glu Gln Gln Ser Ser Ile Asn Ile Ser Gly Tyr
225 230 235 240
Asn Phe Ser Leu Gly Ala Ala Val Lys Ala Gly Ala Ala Leu Leu Asp
245 250 255
Gly Gly Asn Met Leu Glu Ser Ile Leu Ile Lys Pro Ser Asn Ser Glu
260 265 270
Asp Leu Leu Lys Ala Val Leu Gly Ala Lys Lys Lys Leu Asn Met Phe
275 280 285
Val Ser Asp Gln Val Gly Asp Arg Asn Pro Tyr Glu Asn Ile Leu Tyr
290 295 300
Lys Val Cys Leu Ser Gly Glu Gly Trp Pro Tyr Ile Ala Cys Arg Thr
305 310 315 320
Ser Val Val Gly Arg Ala Trp Glu Asn Thr Thr Ile Asp Leu Thr Asn
325 330 335
Glu Lys Leu Val Ala Asn Ser Ser Arg Pro Val Pro Gly Ala Ala Gly
340 345 350
Pro Pro Gln Val Gly Leu Ser Tyr Ser Gln Thr Met Leu Leu Lys Asp
355 360 365
Leu Met Gly Gly Ile Asp Pro Asn Ala Pro Thr Trp Ile Asp Ile Glu
370 375 380
Gly Arg Phe Asn Asp Pro Val Glu Ile Ala Ile Phe Gln Pro Gln Asn
385 390 395 400
Gly Gln Phe Ile His Phe Tyr Arg Glu Pro Thr Asp Gln Lys Gln Phe
405 410 415
Lys Gln Asp Ser Lys Tyr Ser His Gly Met Asp Leu Ala Asp Leu Phe
420 425 430
Asn Ala Gln Pro Gly Leu Thr Ser Ser Val Ile Gly Ala Leu Pro Gln
435 440 445
Gly Met Val Leu Ser Cys Gln Gly Ser Asp Asp Ile Arg Lys Leu Leu
450 455 460
Asp Ser Gln Asn Arg Arg Asp Ile Lys Leu Ile Asp Val Glu Met Thr
465 470 475 480
Lys Glu Ala Ser Arg Glu Tyr Glu Asp Lys Val Trp Asp Lys Tyr Gly
485 490 495
Trp Leu Cys Lys Met His Thr Gly Val Val Arg Asp Lys Lys Lys Lys
500 505 510
Glu Ile Thr Pro His Cys Ala Leu Met Asp Cys Ile Ile Phe Glu Ser
515 520 525
Ala Ser Lys Ala Arg Leu Pro Asp Leu Lys Thr Val His Asn Ile Leu
530 535 540
Pro His Asp Leu Ile Phe Arg Gly Pro Asn Val Val Thr Leu
545 550 555
<210> 13
<211> 273
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(株WE)
<400> 13
atgggccaag gcaagtccaa agaagaaagg gacaccagca atacaggcag agcagagctt 60
ttgccagaca ccacctatct tggtcctcta aattgtaaat catgttggca gaaatttgac 120
agcttggtta gatgccatga ccactatctt tgcagacact gtctgaatct cctgctgtca 180
gtttccgaca gatgtcctct ctgtaagtat ccactgccaa ccaaactgaa ggtgtcaaca 240
gtcccaagct ccccacctcc ctatgaggag tga 273
<210> 14
<211> 90
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(株WE)
<400> 14
Met Gly Gln Gly Lys Ser Lys Glu Glu Arg Asp Thr Ser Asn Thr Gly
1 5 10 15
Arg Ala Glu Leu Leu Pro Asp Thr Thr Tyr Leu Gly Pro Leu Asn Cys
20 25 30
Lys Ser Cys Trp Gln Lys Phe Asp Ser Leu Val Arg Cys His Asp His
35 40 45
Tyr Leu Cys Arg His Cys Leu Asn Leu Leu Leu Ser Val Ser Asp Arg
50 55 60
Cys Pro Leu Cys Lys Tyr Pro Leu Pro Thr Lys Leu Lys Val Ser Thr
65 70 75 80
Val Pro Ser Ser Pro Pro Pro Tyr Glu Glu
85 90
<210> 15
<211> 6630
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(株WE)
<400> 15
atggatgaaa ctattgcaga tttgagagag ttgtgtctaa attacataga acaggacgag 60
aggctgtcaa ggcaaaaact caacttcctg ggacaaagag aacccagaat ggtgctaatt 120
gagggactca aattgttatc acgctgtata gagatagaca gtgcagacaa aagtggttgc 180
atacacaacc acgatgacaa atctgttgaa acaatcctaa tagactctgg gattgtgtgt 240
ccaggactgc cactcatcat ccctgatggt tataagttga ttgacaattc ccttattctt 300
cttgaatgtt ttgttagaag cacaccagct agttttgaaa agaagttcat tgaggacacc 360
aacaaactag catgcatcaa agaagatctt gctgttgcag gcatcacact ggttccaata 420
gtggatggtc gttgtgatta tgataacagt ttcatgccag aatgggtgaa ttttaagttc 480
agagacctcc tatttaaact cctggagtat tctagtcaag atgagaaagt ttttgaggag 540
tctgaatact tcaggctctg tgagtctctt aagaccactg ttgacaaacg ttccggcatg 600
gactcaatga aaattttgaa agacgcaaga tcatttcata acgatgagat tatgaaaatg 660
tgccacgatg gtgtcaaccc caacatgagt tgcgatgatg tggtctttgg cataaattcc 720
ttttttggca ggtttaggag ggacctgtta aatgggaaac tcaaaaggaa tttccaaaag 780
gtcagccctg ggggcttaat caaggaattc tctgaacttt atgaaaccct tactgataat 840
gatgacatat taatgttgag caaagaggca gttgaatcct gccccttaat gaggttcatt 900
acagcagaga cccatgggca tgagagagga agcgatgcta acactgagta tgaaaggcta 960
ctctctatgt tgaacaaggt gaaaagttta aaattattaa acactagaag gagacagctg 1020
ctgaacttag atgtcttatg tctttcttca cttattaagc agtcaatttc caaagggttg 1080
gaaaatgata aacattgggt tggttgttgc tacagtagtg tgaatgatag gcttgtgagc 1140
cttcaaagta ccaaagaaga attcatgaga cttttgaaga acagaagaaa atcaagagtg 1200
cacaaaaagg catctcttga tgagcttttt agggtatcca taaatgagtt catagcaaaa 1260
atccagaaat gcctatcaac agtgggactt agttttgagc attacggact atcagaatgc 1320
ctcgtgcaag aatgccatat accatttgct gaatttgaga actttatgag agccgggact 1380
catcctgtaa tgcattacac aaaatttgaa gattacactt tccagcctaa catagagcaa 1440
ttgaggggtt tacagagttt gagaaaactg tcatctgttt gtttggctct aacaaacagc 1500
atgaaaacaa gctcagttgc aaggttgaga cagaaccaac tggggtctgt gagatatcaa 1560
gtggtggagt gcaaagaggt gttttgccag ataataaaac tggattccga agagtatcat 1620
ctactatatc agaaaactgg agaatcatcg aggtgttatt ccatacaagg tccggatggt 1680
cacttgattt ccttttacgc agatccaaaa aggttctttt taccaatttt ttcagatgag 1740
gtgttgcaca acatgataga cacaatgatt tcatggatta ggtcatgccc tgacttaaaa 1800
gattctctta ttgacattga gactgcacta aggacattga tcctactgat gctcaccaac 1860
ccaacaaaga gaaatcaaaa gcaggttcaa aatattaggt atttagtgat ggccatcgtc 1920
tcagactttt catcgacctc attaatggat aagttgaagg aggatctaat cacacctgcc 1980
gagaaagtgg tgtacaggct gcttcggttt ttgattagga caatttttgg tactggtgaa 2040
aaggtgttat tgagtgcaaa attcaagttt atgttgaatg tgtcatacct gtgtcatttg 2100
atcacaaagg agacccctga tagattgaca gatcagataa aatgttttga aaagttcttt 2160
gagcccaaga gtgagtttgg tttctttgtc aaccctaagg aaacaatcac acccgaagag 2220
gaatgtgttt tttatgaaca aatgaagaag ttcaccggta aagatattga ttgtcagcat 2280
tcaacccctg gtgttaattt agagatcttt agcatgatgg tatcttcatt caacaatggc 2340
accttaattc taaaagggga gaaaaggctc aacaatctgg accccatgac caactctgga 2400
tgtgcgacag cattagatct cgcaagcaac aaaagtgtgg ttgtcaataa acatctgaat 2460
ggagaacggc ttttggagta tgattttaac aaattgcttg ttagtgctgt gagccaaatt 2520
acagagggct tcatgaggaa acaaaagtat aagctgagac actcagatta cgaatataag 2580
gtctcaaagc ttgtctctag attagtcatc ggttccagga aaacagaagt agacaaattg 2640
gaagatgatc cggtagatgt gtgtttcgag ggggaggagg agacaagttt tttcaggagt 2700
ttagaagata aggtcagctc cacaataaca cggtataata gaggcactag gcttaatgaa 2760
gggcaagggg agggagaatt caagaacaca aaaggactac accaccttca gattattttg 2820
tcaggtaaaa gagcttatct gaggaaagtc attttatcag aaatttcatt tcatctagta 2880
gaggactttg atccatcctg tctcaccaat gacgacatga ggtttatttg tgaggctgtt 2940
gaaggttcaa cagaactgtc accattgtat tttacatcag ctgtcaaaga acaatgtggt 3000
ctggatgaga tggcaagaaa cctctgtaga aagttcttct cagagggtga ttggttctca 3060
tgtatgaaga tgatcttgtt acagatgaat gcaaatgcgt attcagggaa gtacagacac 3120
atgcagaggc agagcttaaa ttttaaattt gactgggaca aattggaaga agatgtaaga 3180
attagtgaaa gggaaagcaa ttctgaatct ctaagtaagg ccctttcatt gacaaaatgc 3240
atgagtgctg ctctaaagaa tctgtgtttt tactcagaag aatcaccaac atcatacact 3300
tcagttggcc ctgactctgg gagactaaaa tttgcattgt catacaaaga gcaggttggg 3360
ggaaatagag agctttacat tggggatttg aggacaaaaa tgttcacaag attggtagaa 3420
gattattttg aatccttttc tagtttcttt tcaggatctt gtttaaacaa tgacaaagag 3480
tttgaaaatg caatcttgtc aatgactatc aatgtgagag aagggttgtt aaactacagc 3540
atggatcaca gcaaatgggg accaatgatg tgcccattcc tattcttaat gcttctccaa 3600
aatctcaaac tgggtgatga tcagtacgtg cgttctggaa aagatcatgt tagcaccttg 3660
ttgacttggc atatgcataa acttgttgaa gtccctttcc ctgttgtgaa tgcaatgatg 3720
aaatcatatg ttaaatcaaa actcaagctt ctcaaagggt caggaacgac tgttacggag 3780
agaatcttta gagagtattt tgaaatgggg gtggtgccat ctcacatatc tagtctcatt 3840
gacatgggac aggggatcct acacaatgct tctgattttt acggtttaat tagtgaaagg 3900
tttatcaatt attgtattgg tgtcattttt ggagagaggc cagaagccta tacatcaagt 3960
gatgatcaga tcactttatt tgacaagaga ttgagtgact tagttgatag tgacccagaa 4020
gaagtccttg tcttgctgga attccactct cacttaagtg gtttgttgaa caagttcatc 4080
agtccaaaaa gtgtggttgg gcggtttgca gcggaattca aatccagatt ttatgtgtgg 4140
ggggaggagg tccctctcct cacgaaattt gtgtctgcgg cactacacaa tgttaagtgt 4200
aaagaaccgc atcaactttg tgagacaata gatacgattg ctgatcaagc tatagcaaat 4260
ggagttccag tttttttagt aaactgtatc cagaggagga cactggatct cttgaaatat 4320
gctaatttcc ctttagatcc attcttgtta aacactcaca ctgatgtaaa ggattggtta 4380
gatggttcta gaggttatag aatccaaaga ctcattgaag aattgtgtcc cagtgaaaca 4440
aagatcatga gaaaacttgt aagaagacta catcacaaac tcaagaacgg tgaatgtaac 4500
gaggaatttt ttctagacct cttcaacagg gaaaagaaag aggccatcct tcaattggga 4560
gagattcttg gtcttgagga tgatcttaat gagttggcaa gcatcaattg gttgaatctg 4620
aatgaaatgt tcccattgag gatggttctg agacaaaaag tggtttaccc atcagtaatg 4680
acctttcaag aggaaaagat cccctcattg attaaaacac tccaaaataa gctttgtagt 4740
aagttcacaa gaggtgcaca gaagctgttg tcagaggcaa tcaacaaatc agcttttcag 4800
agttgtgtct catccggctt tataggtctc tgtaagactt taggaagtag gtgtgtgaga 4860
aataaaaaca gggaaaatat gtatatcaga aaggtgcttg aagatctgac catggatgaa 4920
catgtcacaa gggttcacaa acaagatggt gtgatgttgt acatttgcga caagcagaga 4980
cacccagagg ctcaccgtga ccacatcaac cttttgaggc cccttctctg ggactacatt 5040
tgcatctcat tgagcaactc ttttgagctg ggtgtttggg ttttagcaga acctgtgaaa 5100
ggaaagaacg agagtaattc ggctgttagg cacttaaatc catgtgatta tgtagcaaga 5160
aaacctgaga gttcgagact actagaggat aaagtgagtt tgaatcatgt aattcaatct 5220
gtgaggcgac tgtaccccaa aatctttgag gatcagttgc tcccattcat gtctgatgtg 5280
agctcaaaaa atatgagatg gagtcccagg attaaattcc ttgacctttg tgtgctgatt 5340
gacatcaact cagagtcttt gtcactcatt tctcatgttg tcaaatggaa gagggacgaa 5400
cattacactg tgctgttttc tgatctcgtc aactctcacc aacggtcaga ctcaagttta 5460
gttgatgaat ttgttgtcag cacaagggat gtctgcaaga actttttgaa gcaagtgtat 5520
ttcgaatcat ttgtacgaga gtttgttgca acagctagga ccttaggtaa cttttcatgg 5580
ttcccccata aggacatgat gccatctgaa gatggcgctg aagcactggg acccttccaa 5640
tcatttattt tgaaagtggt gaacaagaaa atagagaggc ccatgtttag gaatgacttg 5700
cagtttggtt ttggttggtt ctcttatcgt gtgggggatg ttgtgtgtaa tgccgctatg 5760
ttaattaagc agggtttgac agatccaaaa gcatttaaat ctttaagaga tttgtgggat 5820
tacatgctca gcagcacaga ggggatattg gagttctcaa tcacagtgga tttcacacac 5880
aaccagaaca acactgactg cttgaggaaa ttttcattga tctttgtggt taaatgccaa 5940
ttacagagtc caggtgtagc tgattactta tcgtgctctc atttcttcaa aggtgaggtt 6000
gacaggagat tattagatga gtgtctcaat ctgttgagga cagaccccat ctttaaagcg 6060
aatgatggag tctttgacat taggtctgaa gagtttgaag attacatgga agaccctttg 6120
acacttggtg attcactaga acttgaacta ataggttcta gaaggattct gaatgagatc 6180
aaatctactg actttgagag gatagggcct gagtgggaac ctgtgcctct gaccataagg 6240
aagggtgccc tctttgaggg gaggaacttt gttcagaata tctctgtgaa attggagaca 6300
aaggacatga gggtctttct ggcagagctc gagggctgtg gaaaaattgg tgatgtcctc 6360
ggcagcctcc tcctgcaccg attcagaact ggtgagcact tgatggagtc agaaataagt 6420
acagttcttc aggagctctg catggacaga tccgtcatgc tgacaccatt atcttttgtg 6480
ccagattggt tcaccttcag agattgtagg ctctgcttca gcaggtcaaa gaacactgta 6540
atgtatgaga caactggggg caggttcaga ctcaagggga aatcctgtga cgattggctg 6600
gcggagcggg tggccgagga gatcgactag 6630
<210> 16
<211> 2209
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(株WE)
<400> 16
Met Asp Glu Thr Ile Ala Asp Leu Arg Glu Leu Cys Leu Asn Tyr Ile
1 5 10 15
Glu Gln Asp Glu Arg Leu Ser Arg Gln Lys Leu Asn Phe Leu Gly Gln
20 25 30
Arg Glu Pro Arg Met Val Leu Ile Glu Gly Leu Lys Leu Leu Ser Arg
35 40 45
Cys Ile Glu Ile Asp Ser Ala Asp Lys Ser Gly Cys Ile His Asn His
50 55 60
Asp Asp Lys Ser Val Glu Thr Ile Leu Ile Asp Ser Gly Ile Val Cys
65 70 75 80
Pro Gly Leu Pro Leu Ile Ile Pro Asp Gly Tyr Lys Leu Ile Asp Asn
85 90 95
Ser Leu Ile Leu Leu Glu Cys Phe Val Arg Ser Thr Pro Ala Ser Phe
100 105 110
Glu Lys Lys Phe Ile Glu Asp Thr Asn Lys Leu Ala Cys Ile Lys Glu
115 120 125
Asp Leu Ala Val Ala Gly Ile Thr Leu Val Pro Ile Val Asp Gly Arg
130 135 140
Cys Asp Tyr Asp Asn Ser Phe Met Pro Glu Trp Val Asn Phe Lys Phe
145 150 155 160
Arg Asp Leu Leu Phe Lys Leu Leu Glu Tyr Ser Ser Gln Asp Glu Lys
165 170 175
Val Phe Glu Glu Ser Glu Tyr Phe Arg Leu Cys Glu Ser Leu Lys Thr
180 185 190
Thr Val Asp Lys Arg Ser Gly Met Asp Ser Met Lys Ile Leu Lys Asp
195 200 205
Ala Arg Ser Phe His Asn Asp Glu Ile Met Lys Met Cys His Asp Gly
210 215 220
Val Asn Pro Asn Met Ser Cys Asp Asp Val Val Phe Gly Ile Asn Ser
225 230 235 240
Phe Phe Gly Arg Phe Arg Arg Asp Leu Leu Asn Gly Lys Leu Lys Arg
245 250 255
Asn Phe Gln Lys Val Ser Pro Gly Gly Leu Ile Lys Glu Phe Ser Glu
260 265 270
Leu Tyr Glu Thr Leu Thr Asp Asn Asp Asp Ile Leu Met Leu Ser Lys
275 280 285
Glu Ala Val Glu Ser Cys Pro Leu Met Arg Phe Ile Thr Ala Glu Thr
290 295 300
His Gly His Glu Arg Gly Ser Asp Ala Asn Thr Glu Tyr Glu Arg Leu
305 310 315 320
Leu Ser Met Leu Asn Lys Val Lys Ser Leu Lys Leu Leu Asn Thr Arg
325 330 335
Arg Arg Gln Leu Leu Asn Leu Asp Val Leu Cys Leu Ser Ser Leu Ile
340 345 350
Lys Gln Ser Ile Ser Lys Gly Leu Glu Asn Asp Lys His Trp Val Gly
355 360 365
Cys Cys Tyr Ser Ser Val Asn Asp Arg Leu Val Ser Leu Gln Ser Thr
370 375 380
Lys Glu Glu Phe Met Arg Leu Leu Lys Asn Arg Arg Lys Ser Arg Val
385 390 395 400
His Lys Lys Ala Ser Leu Asp Glu Leu Phe Arg Val Ser Ile Asn Glu
405 410 415
Phe Ile Ala Lys Ile Gln Lys Cys Leu Ser Thr Val Gly Leu Ser Phe
420 425 430
Glu His Tyr Gly Leu Ser Glu Cys Leu Val Gln Glu Cys His Ile Pro
435 440 445
Phe Ala Glu Phe Glu Asn Phe Met Arg Ala Gly Thr His Pro Val Met
450 455 460
His Tyr Thr Lys Phe Glu Asp Tyr Thr Phe Gln Pro Asn Ile Glu Gln
465 470 475 480
Leu Arg Gly Leu Gln Ser Leu Arg Lys Leu Ser Ser Val Cys Leu Ala
485 490 495
Leu Thr Asn Ser Met Lys Thr Ser Ser Val Ala Arg Leu Arg Gln Asn
500 505 510
Gln Leu Gly Ser Val Arg Tyr Gln Val Val Glu Cys Lys Glu Val Phe
515 520 525
Cys Gln Ile Ile Lys Leu Asp Ser Glu Glu Tyr His Leu Leu Tyr Gln
530 535 540
Lys Thr Gly Glu Ser Ser Arg Cys Tyr Ser Ile Gln Gly Pro Asp Gly
545 550 555 560
His Leu Ile Ser Phe Tyr Ala Asp Pro Lys Arg Phe Phe Leu Pro Ile
565 570 575
Phe Ser Asp Glu Val Leu His Asn Met Ile Asp Thr Met Ile Ser Trp
580 585 590
Ile Arg Ser Cys Pro Asp Leu Lys Asp Ser Leu Ile Asp Ile Glu Thr
595 600 605
Ala Leu Arg Thr Leu Ile Leu Leu Met Leu Thr Asn Pro Thr Lys Arg
610 615 620
Asn Gln Lys Gln Val Gln Asn Ile Arg Tyr Leu Val Met Ala Ile Val
625 630 635 640
Ser Asp Phe Ser Ser Thr Ser Leu Met Asp Lys Leu Lys Glu Asp Leu
645 650 655
Ile Thr Pro Ala Glu Lys Val Val Tyr Arg Leu Leu Arg Phe Leu Ile
660 665 670
Arg Thr Ile Phe Gly Thr Gly Glu Lys Val Leu Leu Ser Ala Lys Phe
675 680 685
Lys Phe Met Leu Asn Val Ser Tyr Leu Cys His Leu Ile Thr Lys Glu
690 695 700
Thr Pro Asp Arg Leu Thr Asp Gln Ile Lys Cys Phe Glu Lys Phe Phe
705 710 715 720
Glu Pro Lys Ser Glu Phe Gly Phe Phe Val Asn Pro Lys Glu Thr Ile
725 730 735
Thr Pro Glu Glu Glu Cys Val Phe Tyr Glu Gln Met Lys Lys Phe Thr
740 745 750
Gly Lys Asp Ile Asp Cys Gln His Ser Thr Pro Gly Val Asn Leu Glu
755 760 765
Ile Phe Ser Met Met Val Ser Ser Phe Asn Asn Gly Thr Leu Ile Leu
770 775 780
Lys Gly Glu Lys Arg Leu Asn Asn Leu Asp Pro Met Thr Asn Ser Gly
785 790 795 800
Cys Ala Thr Ala Leu Asp Leu Ala Ser Asn Lys Ser Val Val Val Asn
805 810 815
Lys His Leu Asn Gly Glu Arg Leu Leu Glu Tyr Asp Phe Asn Lys Leu
820 825 830
Leu Val Ser Ala Val Ser Gln Ile Thr Glu Gly Phe Met Arg Lys Gln
835 840 845
Lys Tyr Lys Leu Arg His Ser Asp Tyr Glu Tyr Lys Val Ser Lys Leu
850 855 860
Val Ser Arg Leu Val Ile Gly Ser Arg Lys Thr Glu Val Asp Lys Leu
865 870 875 880
Glu Asp Asp Pro Val Asp Val Cys Phe Glu Gly Glu Glu Glu Thr Ser
885 890 895
Phe Phe Arg Ser Leu Glu Asp Lys Val Ser Ser Thr Ile Thr Arg Tyr
900 905 910
Asn Arg Gly Thr Arg Leu Asn Glu Gly Gln Gly Glu Gly Glu Phe Lys
915 920 925
Asn Thr Lys Gly Leu His His Leu Gln Ile Ile Leu Ser Gly Lys Arg
930 935 940
Ala Tyr Leu Arg Lys Val Ile Leu Ser Glu Ile Ser Phe His Leu Val
945 950 955 960
Glu Asp Phe Asp Pro Ser Cys Leu Thr Asn Asp Asp Met Arg Phe Ile
965 970 975
Cys Glu Ala Val Glu Gly Ser Thr Glu Leu Ser Pro Leu Tyr Phe Thr
980 985 990
Ser Ala Val Lys Glu Gln Cys Gly Leu Asp Glu Met Ala Arg Asn Leu
995 1000 1005
Cys Arg Lys Phe Phe Ser Glu Gly Asp Trp Phe Ser Cys Met Lys
1010 1015 1020
Met Ile Leu Leu Gln Met Asn Ala Asn Ala Tyr Ser Gly Lys Tyr
1025 1030 1035
Arg His Met Gln Arg Gln Ser Leu Asn Phe Lys Phe Asp Trp Asp
1040 1045 1050
Lys Leu Glu Glu Asp Val Arg Ile Ser Glu Arg Glu Ser Asn Ser
1055 1060 1065
Glu Ser Leu Ser Lys Ala Leu Ser Leu Thr Lys Cys Met Ser Ala
1070 1075 1080
Ala Leu Lys Asn Leu Cys Phe Tyr Ser Glu Glu Ser Pro Thr Ser
1085 1090 1095
Tyr Thr Ser Val Gly Pro Asp Ser Gly Arg Leu Lys Phe Ala Leu
1100 1105 1110
Ser Tyr Lys Glu Gln Val Gly Gly Asn Arg Glu Leu Tyr Ile Gly
1115 1120 1125
Asp Leu Arg Thr Lys Met Phe Thr Arg Leu Val Glu Asp Tyr Phe
1130 1135 1140
Glu Ser Phe Ser Ser Phe Phe Ser Gly Ser Cys Leu Asn Asn Asp
1145 1150 1155
Lys Glu Phe Glu Asn Ala Ile Leu Ser Met Thr Ile Asn Val Arg
1160 1165 1170
Glu Gly Leu Leu Asn Tyr Ser Met Asp His Ser Lys Trp Gly Pro
1175 1180 1185
Met Met Cys Pro Phe Leu Phe Leu Met Leu Leu Gln Asn Leu Lys
1190 1195 1200
Leu Gly Asp Asp Gln Tyr Val Arg Ser Gly Lys Asp His Val Ser
1205 1210 1215
Thr Leu Leu Thr Trp His Met His Lys Leu Val Glu Val Pro Phe
1220 1225 1230
Pro Val Val Asn Ala Met Met Lys Ser Tyr Val Lys Ser Lys Leu
1235 1240 1245
Lys Leu Leu Lys Gly Ser Gly Thr Thr Val Thr Glu Arg Ile Phe
1250 1255 1260
Arg Glu Tyr Phe Glu Met Gly Val Val Pro Ser His Ile Ser Ser
1265 1270 1275
Leu Ile Asp Met Gly Gln Gly Ile Leu His Asn Ala Ser Asp Phe
1280 1285 1290
Tyr Gly Leu Ile Ser Glu Arg Phe Ile Asn Tyr Cys Ile Gly Val
1295 1300 1305
Ile Phe Gly Glu Arg Pro Glu Ala Tyr Thr Ser Ser Asp Asp Gln
1310 1315 1320
Ile Thr Leu Phe Asp Lys Arg Leu Ser Asp Leu Val Asp Ser Asp
1325 1330 1335
Pro Glu Glu Val Leu Val Leu Leu Glu Phe His Ser His Leu Ser
1340 1345 1350
Gly Leu Leu Asn Lys Phe Ile Ser Pro Lys Ser Val Val Gly Arg
1355 1360 1365
Phe Ala Ala Glu Phe Lys Ser Arg Phe Tyr Val Trp Gly Glu Glu
1370 1375 1380
Val Pro Leu Leu Thr Lys Phe Val Ser Ala Ala Leu His Asn Val
1385 1390 1395
Lys Cys Lys Glu Pro His Gln Leu Cys Glu Thr Ile Asp Thr Ile
1400 1405 1410
Ala Asp Gln Ala Ile Ala Asn Gly Val Pro Val Phe Leu Val Asn
1415 1420 1425
Cys Ile Gln Arg Arg Thr Leu Asp Leu Leu Lys Tyr Ala Asn Phe
1430 1435 1440
Pro Leu Asp Pro Phe Leu Leu Asn Thr His Thr Asp Val Lys Asp
1445 1450 1455
Trp Leu Asp Gly Ser Arg Gly Tyr Arg Ile Gln Arg Leu Ile Glu
1460 1465 1470
Glu Leu Cys Pro Ser Glu Thr Lys Ile Met Arg Lys Leu Val Arg
1475 1480 1485
Arg Leu His His Lys Leu Lys Asn Gly Glu Cys Asn Glu Glu Phe
1490 1495 1500
Phe Leu Asp Leu Phe Asn Arg Glu Lys Lys Glu Ala Ile Leu Gln
1505 1510 1515
Leu Gly Glu Ile Leu Gly Leu Glu Asp Asp Leu Asn Glu Leu Ala
1520 1525 1530
Ser Ile Asn Trp Leu Asn Leu Asn Glu Met Phe Pro Leu Arg Met
1535 1540 1545
Val Leu Arg Gln Lys Val Val Tyr Pro Ser Val Met Thr Phe Gln
1550 1555 1560
Glu Glu Lys Ile Pro Ser Leu Ile Lys Thr Leu Gln Asn Lys Leu
1565 1570 1575
Cys Ser Lys Phe Thr Arg Gly Ala Gln Lys Leu Leu Ser Glu Ala
1580 1585 1590
Ile Asn Lys Ser Ala Phe Gln Ser Cys Val Ser Ser Gly Phe Ile
1595 1600 1605
Gly Leu Cys Lys Thr Leu Gly Ser Arg Cys Val Arg Asn Lys Asn
1610 1615 1620
Arg Glu Asn Met Tyr Ile Arg Lys Val Leu Glu Asp Leu Thr Met
1625 1630 1635
Asp Glu His Val Thr Arg Val His Lys Gln Asp Gly Val Met Leu
1640 1645 1650
Tyr Ile Cys Asp Lys Gln Arg His Pro Glu Ala His Arg Asp His
1655 1660 1665
Ile Asn Leu Leu Arg Pro Leu Leu Trp Asp Tyr Ile Cys Ile Ser
1670 1675 1680
Leu Ser Asn Ser Phe Glu Leu Gly Val Trp Val Leu Ala Glu Pro
1685 1690 1695
Val Lys Gly Lys Asn Glu Ser Asn Ser Ala Val Arg His Leu Asn
1700 1705 1710
Pro Cys Asp Tyr Val Ala Arg Lys Pro Glu Ser Ser Arg Leu Leu
1715 1720 1725
Glu Asp Lys Val Ser Leu Asn His Val Ile Gln Ser Val Arg Arg
1730 1735 1740
Leu Tyr Pro Lys Ile Phe Glu Asp Gln Leu Leu Pro Phe Met Ser
1745 1750 1755
Asp Val Ser Ser Lys Asn Met Arg Trp Ser Pro Arg Ile Lys Phe
1760 1765 1770
Leu Asp Leu Cys Val Leu Ile Asp Ile Asn Ser Glu Ser Leu Ser
1775 1780 1785
Leu Ile Ser His Val Val Lys Trp Lys Arg Asp Glu His Tyr Thr
1790 1795 1800
Val Leu Phe Ser Asp Leu Val Asn Ser His Gln Arg Ser Asp Ser
1805 1810 1815
Ser Leu Val Asp Glu Phe Val Val Ser Thr Arg Asp Val Cys Lys
1820 1825 1830
Asn Phe Leu Lys Gln Val Tyr Phe Glu Ser Phe Val Arg Glu Phe
1835 1840 1845
Val Ala Thr Ala Arg Thr Leu Gly Asn Phe Ser Trp Phe Pro His
1850 1855 1860
Lys Asp Met Met Pro Ser Glu Asp Gly Ala Glu Ala Leu Gly Pro
1865 1870 1875
Phe Gln Ser Phe Ile Leu Lys Val Val Asn Lys Lys Ile Glu Arg
1880 1885 1890
Pro Met Phe Arg Asn Asp Leu Gln Phe Gly Phe Gly Trp Phe Ser
1895 1900 1905
Tyr Arg Val Gly Asp Val Val Cys Asn Ala Ala Met Leu Ile Lys
1910 1915 1920
Gln Gly Leu Thr Asp Pro Lys Ala Phe Lys Ser Leu Arg Asp Leu
1925 1930 1935
Trp Asp Tyr Met Leu Ser Ser Thr Glu Gly Ile Leu Glu Phe Ser
1940 1945 1950
Ile Thr Val Asp Phe Thr His Asn Gln Asn Asn Thr Asp Cys Leu
1955 1960 1965
Arg Lys Phe Ser Leu Ile Phe Val Val Lys Cys Gln Leu Gln Ser
1970 1975 1980
Pro Gly Val Ala Asp Tyr Leu Ser Cys Ser His Phe Phe Lys Gly
1985 1990 1995
Glu Val Asp Arg Arg Leu Leu Asp Glu Cys Leu Asn Leu Leu Arg
2000 2005 2010
Thr Asp Pro Ile Phe Lys Ala Asn Asp Gly Val Phe Asp Ile Arg
2015 2020 2025
Ser Glu Glu Phe Glu Asp Tyr Met Glu Asp Pro Leu Thr Leu Gly
2030 2035 2040
Asp Ser Leu Glu Leu Glu Leu Ile Gly Ser Arg Arg Ile Leu Asn
2045 2050 2055
Glu Ile Lys Ser Thr Asp Phe Glu Arg Ile Gly Pro Glu Trp Glu
2060 2065 2070
Pro Val Pro Leu Thr Ile Arg Lys Gly Ala Leu Phe Glu Gly Arg
2075 2080 2085
Asn Phe Val Gln Asn Ile Ser Val Lys Leu Glu Thr Lys Asp Met
2090 2095 2100
Arg Val Phe Leu Ala Glu Leu Glu Gly Cys Gly Lys Ile Gly Asp
2105 2110 2115
Val Leu Gly Ser Leu Leu Leu His Arg Phe Arg Thr Gly Glu His
2120 2125 2130
Leu Met Glu Ser Glu Ile Ser Thr Val Leu Gln Glu Leu Cys Met
2135 2140 2145
Asp Arg Ser Val Met Leu Thr Pro Leu Ser Phe Val Pro Asp Trp
2150 2155 2160
Phe Thr Phe Arg Asp Cys Arg Leu Cys Phe Ser Arg Ser Lys Asn
2165 2170 2175
Thr Val Met Tyr Glu Thr Thr Gly Gly Arg Phe Arg Leu Lys Gly
2180 2185 2190
Lys Ser Cys Asp Asp Trp Leu Ala Glu Arg Val Ala Glu Glu Ile
2195 2200 2205
Asp
<210> 17
<211> 1497
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P42)
<400> 17
atgggtcaga ttgtgacaat gtttgaggct ttgcctcaca tcattgatga ggtcatcaac 60
attgtcatta ttgtgctcat tataatcacg agcatcaaag ctgtgtacaa tttcgccacc 120
tgtgggatat tagcactggt cagcttcctt tttttggctg gtaggtcctg tggcatgtac 180
ggccttaatg gtcccgacat ctataaaggg gtttaccagt tcaaatcagt ggagtttgat 240
atgtctcact taaatctgac gatgcccaat gcgtgctcag ccaacaactc tcatcactac 300
atcagtatgg gaagctctgg actggagcta actttcacta acgactccat ccttaatcac 360
aatttttgca acttaacctc cgctttcaac aaaaagactt ttgaccatac actcatgagt 420
atagtctcga gtctgcacct cagtattaga gggaattcca accacaaagc agtgtcttgt 480
gattttaaca atggcatcac cattcaatac aacttgtcat tttcggaccc acagagcgct 540
atgagccagt gtaggacttt cagaggtaga gtcttggaca tgtttagaac tgcctttgga 600
ggaaaataca tgagaagtgg ctggggctgg gcaggttcag atggcaagac cacttggtgc 660
agccaaacaa gctatcagta cctaatcata caaaacagga cttgggaaaa ccactgtaga 720
tatgcaggcc cttttgggat gtctagaatc ctctttgctc aggaaaagac aaagtttctc 780
actaggagac ttgcaggcac attcacctgg accctgtcag actcctcagg agtagaaaat 840
ccaggtggtt attgcctgac caaatggatg atccttgctg cagagctcaa atgttttggg 900
aatacagctg ttgcaaaatg taatgtcaat catgatgaag agttctgtga catgctacga 960
ctaattgatt acaacaaggc cgccctgagt aagttcaagc aagatgtaga gtctgccttg 1020
catgtattca aaacaacagt aaattctctg atttccgatc agctgttgat gaggaatcat 1080
ctaagagatc taatgggggt accatactgt aattactcaa agttctggta tctggaacat 1140
gctaagactg gtgagactag tgtacccaag tgctggcttg tcactaatgg ctcctacttg 1200
aatgagaccc actttagtga tcaaatcgaa caagaagcag ataacatgat cacagagatg 1260
ttgaggaagg actacataaa aagacaaggg agtactcctt tagccttaat ggatcttttg 1320
atgttttcaa catcagcata tctaatcagc atctttctgc atcttgtgaa gataccaaca 1380
catagacaca taaagggcgg ttcatgtcca aagccacacc gcttgaccaa caaggggatc 1440
tgtagttgtg gtgcattcaa ggtgcctggt gtaaaaacta tctggaaaag acgctga 1497
<210> 18
<211> 498
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P42)
<400> 18
Met Gly Gln Ile Val Thr Met Phe Glu Ala Leu Pro His Ile Ile Asp
1 5 10 15
Glu Val Ile Asn Ile Val Ile Ile Val Leu Ile Ile Ile Thr Ser Ile
20 25 30
Lys Ala Val Tyr Asn Phe Ala Thr Cys Gly Ile Leu Ala Leu Val Ser
35 40 45
Phe Leu Phe Leu Ala Gly Arg Ser Cys Gly Met Tyr Gly Leu Asn Gly
50 55 60
Pro Asp Ile Tyr Lys Gly Val Tyr Gln Phe Lys Ser Val Glu Phe Asp
65 70 75 80
Met Ser His Leu Asn Leu Thr Met Pro Asn Ala Cys Ser Ala Asn Asn
85 90 95
Ser His His Tyr Ile Ser Met Gly Ser Ser Gly Leu Glu Leu Thr Phe
100 105 110
Thr Asn Asp Ser Ile Leu Asn His Asn Phe Cys Asn Leu Thr Ser Ala
115 120 125
Phe Asn Lys Lys Thr Phe Asp His Thr Leu Met Ser Ile Val Ser Ser
130 135 140
Leu His Leu Ser Ile Arg Gly Asn Ser Asn His Lys Ala Val Ser Cys
145 150 155 160
Asp Phe Asn Asn Gly Ile Thr Ile Gln Tyr Asn Leu Ser Phe Ser Asp
165 170 175
Pro Gln Ser Ala Met Ser Gln Cys Arg Thr Phe Arg Gly Arg Val Leu
180 185 190
Asp Met Phe Arg Thr Ala Phe Gly Gly Lys Tyr Met Arg Ser Gly Trp
195 200 205
Gly Trp Ala Gly Ser Asp Gly Lys Thr Thr Trp Cys Ser Gln Thr Ser
210 215 220
Tyr Gln Tyr Leu Ile Ile Gln Asn Arg Thr Trp Glu Asn His Cys Arg
225 230 235 240
Tyr Ala Gly Pro Phe Gly Met Ser Arg Ile Leu Phe Ala Gln Glu Lys
245 250 255
Thr Lys Phe Leu Thr Arg Arg Leu Ala Gly Thr Phe Thr Trp Thr Leu
260 265 270
Ser Asp Ser Ser Gly Val Glu Asn Pro Gly Gly Tyr Cys Leu Thr Lys
275 280 285
Trp Met Ile Leu Ala Ala Glu Leu Lys Cys Phe Gly Asn Thr Ala Val
290 295 300
Ala Lys Cys Asn Val Asn His Asp Glu Glu Phe Cys Asp Met Leu Arg
305 310 315 320
Leu Ile Asp Tyr Asn Lys Ala Ala Leu Ser Lys Phe Lys Gln Asp Val
325 330 335
Glu Ser Ala Leu His Val Phe Lys Thr Thr Val Asn Ser Leu Ile Ser
340 345 350
Asp Gln Leu Leu Met Arg Asn His Leu Arg Asp Leu Met Gly Val Pro
355 360 365
Tyr Cys Asn Tyr Ser Lys Phe Trp Tyr Leu Glu His Ala Lys Thr Gly
370 375 380
Glu Thr Ser Val Pro Lys Cys Trp Leu Val Thr Asn Gly Ser Tyr Leu
385 390 395 400
Asn Glu Thr His Phe Ser Asp Gln Ile Glu Gln Glu Ala Asp Asn Met
405 410 415
Ile Thr Glu Met Leu Arg Lys Asp Tyr Ile Lys Arg Gln Gly Ser Thr
420 425 430
Pro Leu Ala Leu Met Asp Leu Leu Met Phe Ser Thr Ser Ala Tyr Leu
435 440 445
Ile Ser Ile Phe Leu His Leu Val Lys Ile Pro Thr His Arg His Ile
450 455 460
Lys Gly Gly Ser Cys Pro Lys Pro His Arg Leu Thr Asn Lys Gly Ile
465 470 475 480
Cys Ser Cys Gly Ala Phe Lys Val Pro Gly Val Lys Thr Ile Trp Lys
485 490 495
Arg Arg
<210> 19
<211> 1677
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P42)
<400> 19
atgtctttgt ccaaagaagt caaaagcttt cagtggacac aggcgttgag gagggagttg 60
cagagtttta catcagatgt aaaggctgcc gtcatcaagg acgcaaccag tcttctaaat 120
gggttggact tttctgaagt cagcaacgtt cagaggatca tgagaaagga aaggagggat 180
gataaagact tgcagagact caggagtctt aaccagactg tgcattctct tgttgatctg 240
aagtctacat caaagaaaaa tgttctgaaa gtgggaagac ttagtgcaga ggaattgatg 300
acccttgcag ctgatcttga gaagctgaag gccaaaatta tgagaactga gaggcctcaa 360
gcttctggag tctacatggg aaatttgaca gcacaacaac ttgatcaaag atcccaaata 420
ctgcaaatgg ttgggatgag aagacctcag cagggtgcaa gtggtgtagt aagggtttgg 480
gatgtgaagg actcatcact tctgaacaat cagttcggca caatgccaag cctgacaatg 540
gcttgcatgg caaaacagtc acagacccca ctcaatgatg ttgtgcaggc actcacagac 600
cttggcttac tttacacagt caaatacccg aatctcagtg atcttgaaag gctaaaggat 660
aaacacccag ttctgggggt cattactgaa cagcaatcta gtatcaatat ctctggttat 720
aatttcagtc ttggtgcagc tgtgaaagcg ggggcagctc tgctagatgg agggaacatg 780
ctggaatcta tcttgatcaa accgagcaac agtgaggatc tcctaaaagc agtcctcggg 840
gccaagaaga aactcaacat gtttgtctca gatcaagttg gagatagaaa tccctatgaa 900
aacatccttt ataaagtctg tctttcaggt gaaggatggc catacatagc ctgtagaacg 960
tcagttgtgg ggagagcatg ggagaacaca acaattgatc tcacaaatga aaaacttgtt 1020
gccaactcat ctaggccagt gcctggagca gcaggcccac ctcaggtggg cttgagttac 1080
agtcagacaa tgctgttgaa agacttgatg ggagggattg atcccaatgc tcccacatgg 1140
attgacattg agggcaggtt caatgatcca gtggagatag caatattcca accacaaaat 1200
gggcaattca tacattttta cagggaacct acggaccaga agcaattcaa gcaggactca 1260
aagtattcac acggcatgga tcttgctgat ctcttcaatg cacagcctgg gctgacctca 1320
tcagttatag gtgctctccc acaagggatg gttttgagct gtcaaggttc tgatgacatc 1380
agaaagcttc tggactcaca aaatagaagg gacataaaac tcattgatgt tgagatgacc 1440
aaggaggcct caagagaata tgaagataaa gtgtgggaca aatatggctg gctatgcaaa 1500
atgcacactg gggtagtgag agacaaaaag aagaaagaga tcaccccaca ctgtgcactc 1560
atggactgca tcatttttga gagtgcttcc aaggcaagac tccctgatct aaaaaccgtt 1620
cacaacatcc tgccacatga tttaatcttc agaggaccca atgttgtgac actctaa 1677
<210> 20
<211> 558
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P42)
<400> 20
Met Ser Leu Ser Lys Glu Val Lys Ser Phe Gln Trp Thr Gln Ala Leu
1 5 10 15
Arg Arg Glu Leu Gln Ser Phe Thr Ser Asp Val Lys Ala Ala Val Ile
20 25 30
Lys Asp Ala Thr Ser Leu Leu Asn Gly Leu Asp Phe Ser Glu Val Ser
35 40 45
Asn Val Gln Arg Ile Met Arg Lys Glu Arg Arg Asp Asp Lys Asp Leu
50 55 60
Gln Arg Leu Arg Ser Leu Asn Gln Thr Val His Ser Leu Val Asp Leu
65 70 75 80
Lys Ser Thr Ser Lys Lys Asn Val Leu Lys Val Gly Arg Leu Ser Ala
85 90 95
Glu Glu Leu Met Thr Leu Ala Ala Asp Leu Glu Lys Leu Lys Ala Lys
100 105 110
Ile Met Arg Thr Glu Arg Pro Gln Ala Ser Gly Val Tyr Met Gly Asn
115 120 125
Leu Thr Ala Gln Gln Leu Asp Gln Arg Ser Gln Ile Leu Gln Met Val
130 135 140
Gly Met Arg Arg Pro Gln Gln Gly Ala Ser Gly Val Val Arg Val Trp
145 150 155 160
Asp Val Lys Asp Ser Ser Leu Leu Asn Asn Gln Phe Gly Thr Met Pro
165 170 175
Ser Leu Thr Met Ala Cys Met Ala Lys Gln Ser Gln Thr Pro Leu Asn
180 185 190
Asp Val Val Gln Ala Leu Thr Asp Leu Gly Leu Leu Tyr Thr Val Lys
195 200 205
Tyr Pro Asn Leu Ser Asp Leu Glu Arg Leu Lys Asp Lys His Pro Val
210 215 220
Leu Gly Val Ile Thr Glu Gln Gln Ser Ser Ile Asn Ile Ser Gly Tyr
225 230 235 240
Asn Phe Ser Leu Gly Ala Ala Val Lys Ala Gly Ala Ala Leu Leu Asp
245 250 255
Gly Gly Asn Met Leu Glu Ser Ile Leu Ile Lys Pro Ser Asn Ser Glu
260 265 270
Asp Leu Leu Lys Ala Val Leu Gly Ala Lys Lys Lys Leu Asn Met Phe
275 280 285
Val Ser Asp Gln Val Gly Asp Arg Asn Pro Tyr Glu Asn Ile Leu Tyr
290 295 300
Lys Val Cys Leu Ser Gly Glu Gly Trp Pro Tyr Ile Ala Cys Arg Thr
305 310 315 320
Ser Val Val Gly Arg Ala Trp Glu Asn Thr Thr Ile Asp Leu Thr Asn
325 330 335
Glu Lys Leu Val Ala Asn Ser Ser Arg Pro Val Pro Gly Ala Ala Gly
340 345 350
Pro Pro Gln Val Gly Leu Ser Tyr Ser Gln Thr Met Leu Leu Lys Asp
355 360 365
Leu Met Gly Gly Ile Asp Pro Asn Ala Pro Thr Trp Ile Asp Ile Glu
370 375 380
Gly Arg Phe Asn Asp Pro Val Glu Ile Ala Ile Phe Gln Pro Gln Asn
385 390 395 400
Gly Gln Phe Ile His Phe Tyr Arg Glu Pro Thr Asp Gln Lys Gln Phe
405 410 415
Lys Gln Asp Ser Lys Tyr Ser His Gly Met Asp Leu Ala Asp Leu Phe
420 425 430
Asn Ala Gln Pro Gly Leu Thr Ser Ser Val Ile Gly Ala Leu Pro Gln
435 440 445
Gly Met Val Leu Ser Cys Gln Gly Ser Asp Asp Ile Arg Lys Leu Leu
450 455 460
Asp Ser Gln Asn Arg Arg Asp Ile Lys Leu Ile Asp Val Glu Met Thr
465 470 475 480
Lys Glu Ala Ser Arg Glu Tyr Glu Asp Lys Val Trp Asp Lys Tyr Gly
485 490 495
Trp Leu Cys Lys Met His Thr Gly Val Val Arg Asp Lys Lys Lys Lys
500 505 510
Glu Ile Thr Pro His Cys Ala Leu Met Asp Cys Ile Ile Phe Glu Ser
515 520 525
Ala Ser Lys Ala Arg Leu Pro Asp Leu Lys Thr Val His Asn Ile Leu
530 535 540
Pro His Asp Leu Ile Phe Arg Gly Pro Asn Val Val Thr Leu
545 550 555
<210> 21
<211> 273
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P42)
<400> 21
atgggccaag gcaagtccaa agaagaaagg gacaccagca atacaggcag agcagagctt 60
ttgccagaca ccacctatct tggtcctcta aattgtaaat catgttggca gaaatttgac 120
agcttggtta gatgccatga ccactatctt tgcagacact gtctgaatct cctgctgtca 180
gtttccgaca gatgtcctct ctgtaagtat ccactgccaa ccaaactgaa ggtgtcaaca 240
gtcccaagct ccccacctcc ctatgaggag tga 273
<210> 22
<211> 90
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P42)
<400> 22
Met Gly Gln Gly Lys Ser Lys Glu Glu Arg Asp Thr Ser Asn Thr Gly
1 5 10 15
Arg Ala Glu Leu Leu Pro Asp Thr Thr Tyr Leu Gly Pro Leu Asn Cys
20 25 30
Lys Ser Cys Trp Gln Lys Phe Asp Ser Leu Val Arg Cys His Asp His
35 40 45
Tyr Leu Cys Arg His Cys Leu Asn Leu Leu Leu Ser Val Ser Asp Arg
50 55 60
Cys Pro Leu Cys Lys Tyr Pro Leu Pro Thr Lys Leu Lys Val Ser Thr
65 70 75 80
Val Pro Ser Ser Pro Pro Pro Tyr Glu Glu
85 90
<210> 23
<211> 6630
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P42)
<400> 23
atggatgaaa ctattgcaga tttgagagag ttgtgtctaa attacataga acaggacgag 60
aggctgtcaa ggcaaaaact caacttcctg ggacaaagag aacccagaat ggtgctaatt 120
gagggactca aattgttatc acgctgtata gagatagaca gtgcagacaa aagtggttgc 180
atacacaacc acgatgacaa atctgttgaa acaatcctaa tagactctgg gattgtgtgt 240
ccaggactgc cactcatcat ccctgatggt tataagttga ttgacaattc ccttattctt 300
cttgaatgtt ttgttagaag cacaccagct agttttgaaa agaagttcat tgaggacacc 360
aacaaactag catgcatcaa agaagatctt gctgttgcag gcatcacact ggttccaata 420
gtggatggtc gttgtgatta tgataacagt ttcatgccag aatgggtgaa ttttaagttc 480
agagacctcc tatttaaact cctggagtat tctagtcaag atgagaaagt ttttgaggag 540
tctgaatact tcaggctctg tgagtctctt aagaccactg ttgacaaacg ttccggcatg 600
gactcaatga aaattttgaa agacgcaaga tcatttcata acgatgagat tatgaaaatg 660
tgccacgatg gtgtcaaccc caacatgagt tgcgatgatg tggtctttgg cataaattcc 720
ttttttggca ggtttaggag ggacctgtta aatgggaaac tcaaaaggaa tttccaaaag 780
gtcagccctg ggggcttaat caaggaattc tctgaacttt atgaaaccct tactgataat 840
gatgacatat taatgttgag caaagaggca gttgaatcct gccccttaat gaggttcatt 900
acagcagaga cccatgggca tgagagagga agcgatgcta acactgagta tgaaaggcta 960
ctctctatgt tgaacaaggt gaaaagttta aaattattaa acactagaag gagacagctg 1020
ctgaacttag atgtcttatg tctttcttca cttattaagc agtcaatttc caaagggttg 1080
gaaaatgata aacattgggt tggttgttgc tacagtagtg tgaatgatag gcttgtgagc 1140
cttcaaagta ccaaagaaga attcatgaga cttttgaaga acagaagaaa atcaagagtg 1200
cacaaaaagg catctcttga tgagcttttt agggtatcca taaatgagtt catagcaaaa 1260
atccagaaat gcctatcaac agtgggactt agttttgagc attacggact atcagaatgc 1320
ctcgtgcaag aatgccatat accatttgct gaatttgaga actttatgag agccgggact 1380
catcctgtaa tgcattacac aaaatttgaa gattacactt tccagcctaa catagagcaa 1440
ttgaggggtt tacagagttt gagaaaactg tcatctgttt gtttggctct aacaaacagc 1500
atgaaaacaa gctcagttgc aaggttgaga cagaaccaac tggggtctgt gagatatcaa 1560
gtggtggagt gcaaagaggt gttttgccag ataataaaac tggattccga agagtatcat 1620
ctactatatc agaaaactgg agaatcatcg aggtgttatt ccatacaagg tccggatggt 1680
cacttgattt ccttttacgc agatccaaaa aggttctttt taccaatttt ttcagatgag 1740
gtgttgcaca acatgataga cacaatgatt tcatggatta ggtcatgccc tgacttaaaa 1800
gattctctta ttgacattga gactgcacta aggacattga tcctactgat gctcaccaac 1860
ccaacaaaga gaaatcaaaa gcaggttcaa aatattaggt atttagtgat ggccatcgtc 1920
tcagactttt catcgacctc attaatggat aagttgaagg aggatctaat cacacctgcc 1980
gagaaagtgg tgtacaggct gcttcggttt ttgattagga caatttttgg tactggtgaa 2040
aaggtgttat tgagtgcaaa attcaagttt atgttgaatg tgtcatacct gtgtcatttg 2100
atcacaaagg agacccctga tagattgaca gatcagataa aatgttttga aaagttcttt 2160
gagcccaaga gtgagtttgg tttctttgtc aaccctaagg aaacaatcac acccgaagag 2220
gaatgtgttt tttatgaaca aatgaagaag ttcaccggta aagatattga ttgtcagcat 2280
tcaacccctg gtgttaattt agagatcttt agcatgatgg tatcttcatt caacaatggc 2340
accttaattc taaaagggga gaaaaggctc aacaatctgg accccatgac caactctgga 2400
tgtgcgacag cattagatct cgcaagcaac aaaagtgtgg ttgtcaataa acatctgaat 2460
ggagaacggc ttttggagta tgattttaac aaattgcttg ttagtgctgt gagccaaatt 2520
acagagggct tcatgaggaa acaaaagtat aagctgagac actcagatta cgaatataag 2580
gtctcaaagc ttgtctctag attagtcatc ggttccagga aaacagaagt agacaaattg 2640
gaagatgatc cggtagatgt gtgtttcgag ggggaggagg agacaagttt tttcaggagt 2700
ttagaagata aggtcagctc cacaataaca cggtataata gaggcactag gcttaatgaa 2760
gggcaagggg agggagaatt caagaacaca aaaggactac accaccttca gattattttg 2820
tcaggtaaaa gagcttatct gaggaaagtc attttatcag aaatttcatt tcatctagta 2880
gaggactttg atccatcctg tctcaccaat gacgacatga ggtttatttg tgaggctgtt 2940
gaaggttcaa cagaactgtc accattgtat tttacatcag ctgtcaaaga acaatgtggt 3000
ctggatgaga tggcaagaaa cctctgtaga aagttcttct cagagggtga ttggttctca 3060
tgtatgaaga tgatcttgtt acagatgaat gcaaatgcgt attcagggaa gtacagacac 3120
atgcagaggc agagcttaaa ttttaaattt gactgggaca aattggaaga agatgtaaga 3180
attagtgaaa gggaaagcaa ttctgaatct ctaagtaagg ccctttcatt gacaaaatgc 3240
atgagtgctg ctctaaagaa tctgtgtttt tactcagaag aatcaccaac atcatacact 3300
tcagttggcc ctgactctgg gagactaaaa tttgcattgt catacaaaga gcaggttggg 3360
ggaaatagag agctttacat tggggatttg aggacaaaaa tgttcacaag attggtagaa 3420
gattattttg aatccttttc tagtttcttt tcaggatctt gtttaaacaa tgacaaagag 3480
tttgaaaatg caatcttgtc aatgactatc aatgtgagag aagggttgtt aaactacagc 3540
atggatcaca gcaaatgggg accaatgatg tgcccattcc tattcttaat gctyctccaa 3600
aatctcaaac tgggtgatga tcagtacgtg cgttctggaa aagatcatgt tagcaccttg 3660
ttgacttggc atatgcataa acttgttgaa gtccctttcc ctgttgtgaa tgcaatgatg 3720
aaatcatatg ttaaatcaaa actcaagctt ctcaaagggt caggaacgac tgttacggag 3780
agaatcttta gagagtattt tgaaatgggg gtggtgccat ctcacatatc tagtctcatt 3840
gacatgggac aggggatcct acacaatgct tctgattttt acggtttaat tagtgaaagg 3900
tttatcaatt attgtattgg tgtcattttt ggagagaggc cagaagccta tacatcaagt 3960
gatgatcaga tcactttatt tgacaagaga ttgagtgact tagttgatag tgacccagaa 4020
gaagtccttg tcttgctgga attccactct cacttaagtg gtttgttgaa caagttcatc 4080
agtccaaaaa gtgtggttgg gcggtttgca gcggaattca aatccagatt ttatgtgtgg 4140
ggggaggagg tccctctcct cacgaaattt gtgtctgcgg cactacacaa tgttaagtgt 4200
aaagaaccgc atcaactttg tgagacaata gatacgattg ctgatcaagc tatagcaaat 4260
ggagttccag tttttttagt aaactgtatc cagaggagga cactggatct cttgaaatat 4320
gctaatttcc ctttagatcc attcttgtta aacactcaca ctgatgtaaa ggattggtta 4380
gatggttcta gaggttatag aatccaaaga ctcattgaag aattgtgtcc cagtgaaaca 4440
aagatcatga gaaaacttgt aagaagacta catcacaaac tcaagaacgg tgaatgtaac 4500
gaggaatttt ttctagacct cttcaacagg gaaaagaaag aggccatcct tcaattggga 4560
gagattcttg gtcttgagga tgatcttaat gagttggcaa gcatcaattg gttgaatctg 4620
aatgaaatgt tcccattgag gatggttctg agacaaaaag tggtttaccc atcagtratg 4680
acctttcaag aggaaaagat cccctcattg attaaaacac tccaaaataa gctttgtagt 4740
aagttcacaa gaggtgcaca gaagctgttg tcagaggcaa tcaacaaatc agcttttcag 4800
agttgtgtct catccggctt tataggtctc tgtaagactt taggaagtag gtgtgtgaga 4860
aataaaaaca gggaaaatat gtatatcaga aaggtgcttg aagatctgac catggatgaa 4920
catgtcacaa gggttcacaa acaagatggt gtgatgttgt acatttgcga caagcagaga 4980
cacccagagg ctcaccgtga ccacatcaac cttttgaggc cccttctctg ggactacatt 5040
tgcatctcat tgagcaactc ttttgagctg ggtgtttggg ttttagcaga acctgtgaaa 5100
ggaaagaacg agagtaattc ggctgttagg cacttaaatc catgtgatta tgtagcaaga 5160
aaacctgaga gttcgagact actagaggat aaagtgagtt tgaatcatgt aattcaatct 5220
gtgaggcgac tgtaccccaa aatctttgag gatcagttgc tcccattcat gtttgatgtg 5280
agctcaaaaa atatgagatg gagtcccagg attaaattcc ttgacctttg tgtgctgatt 5340
gacatcaact cagagtcttt gtcactcatt tctcatgttg tcaaatggaa gagggacgaa 5400
cattacactg tgctgttttc tgatctcgtc aactctcacc aacggtcaga ctcaagttta 5460
gttgatgaat ttgttgtcag cacaagggat gtctgcaaga actttttgaa gcaagtgtat 5520
ttcgaatcat ttgtacgaga gtttgttgca acagctagga ccttaggtaa cttttcatgg 5580
ttcccccata aggacatgat gccatctgaa gatggcgctg aagcactggg acccttccaa 5640
tcatttattt tgaaagtggt gaacaagaaa atagagaggc ccatgtttag gaatgacttg 5700
cagtttggtt ttggttggtt ctcttatcgt gtgggggatg ttgtgtgtaa tgccgctatg 5760
ttaattaagc agggtttgac agatccaaaa gcatttaaat ctttaagaga tttgtgggat 5820
tacatgctca gcagcacaga ggggatattg gagttctcaa tcacagtgga tttcacacac 5880
aaccagaaca acactgactg cttgaggaaa ttttcattga tctttgtggt taaatgccaa 5940
ttacagagtc caggtgtagc tgattactta tcgtgctctc atttcttcaa aggtgaggtt 6000
gacaggagat tattagatga gtgtctcaat ctgttgagga cagaccccat ctttaaagcg 6060
aatgatggag tctttgacat taggtctgaa gagtttgaag attacatgga agaccctttg 6120
acacttggtg attcactaga acttgaacta ataggttcta gaaggattct gaatgagatc 6180
aaatctactg actttgagag gatagggcct gagtgggaac ctgtgcctct gaccataagg 6240
aagggtgccc tctttgaggg gaggaacttt gttcagaata tctctgtgaa attggagaca 6300
aaggacatga grgtctttct ggcagagctc gagggctgtg gaaaaattgg tgatgtcctc 6360
ggcagcctcc tcctgcaccg attcagaact ggtgagcact tgatggagtc agaaataagt 6420
acagttcttc aggagctctg catggacaga tccgtcatgc tgacaccatt atcttttgtg 6480
ccagattggt tcaccttcag agattgtagg ctctgcttca gcaggtcaaa gaacactgtr 6540
atgtatgaga caactggggg caggttcaga ctcaagggga aatcctgtga cgattggctg 6600
gcggagcggg tggccgagga gatcgactag 6630
<210> 24
<211> 2209
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P42)
<400> 24
Met Asp Glu Thr Ile Ala Asp Leu Arg Glu Leu Cys Leu Asn Tyr Ile
1 5 10 15
Glu Gln Asp Glu Arg Leu Ser Arg Gln Lys Leu Asn Phe Leu Gly Gln
20 25 30
Arg Glu Pro Arg Met Val Leu Ile Glu Gly Leu Lys Leu Leu Ser Arg
35 40 45
Cys Ile Glu Ile Asp Ser Ala Asp Lys Ser Gly Cys Ile His Asn His
50 55 60
Asp Asp Lys Ser Val Glu Thr Ile Leu Ile Asp Ser Gly Ile Val Cys
65 70 75 80
Pro Gly Leu Pro Leu Ile Ile Pro Asp Gly Tyr Lys Leu Ile Asp Asn
85 90 95
Ser Leu Ile Leu Leu Glu Cys Phe Val Arg Ser Thr Pro Ala Ser Phe
100 105 110
Glu Lys Lys Phe Ile Glu Asp Thr Asn Lys Leu Ala Cys Ile Lys Glu
115 120 125
Asp Leu Ala Val Ala Gly Ile Thr Leu Val Pro Ile Val Asp Gly Arg
130 135 140
Cys Asp Tyr Asp Asn Ser Phe Met Pro Glu Trp Val Asn Phe Lys Phe
145 150 155 160
Arg Asp Leu Leu Phe Lys Leu Leu Glu Tyr Ser Ser Gln Asp Glu Lys
165 170 175
Val Phe Glu Glu Ser Glu Tyr Phe Arg Leu Cys Glu Ser Leu Lys Thr
180 185 190
Thr Val Asp Lys Arg Ser Gly Met Asp Ser Met Lys Ile Leu Lys Asp
195 200 205
Ala Arg Ser Phe His Asn Asp Glu Ile Met Lys Met Cys His Asp Gly
210 215 220
Val Asn Pro Asn Met Ser Cys Asp Asp Val Val Phe Gly Ile Asn Ser
225 230 235 240
Phe Phe Gly Arg Phe Arg Arg Asp Leu Leu Asn Gly Lys Leu Lys Arg
245 250 255
Asn Phe Gln Lys Val Ser Pro Gly Gly Leu Ile Lys Glu Phe Ser Glu
260 265 270
Leu Tyr Glu Thr Leu Thr Asp Asn Asp Asp Ile Leu Met Leu Ser Lys
275 280 285
Glu Ala Val Glu Ser Cys Pro Leu Met Arg Phe Ile Thr Ala Glu Thr
290 295 300
His Gly His Glu Arg Gly Ser Asp Ala Asn Thr Glu Tyr Glu Arg Leu
305 310 315 320
Leu Ser Met Leu Asn Lys Val Lys Ser Leu Lys Leu Leu Asn Thr Arg
325 330 335
Arg Arg Gln Leu Leu Asn Leu Asp Val Leu Cys Leu Ser Ser Leu Ile
340 345 350
Lys Gln Ser Ile Ser Lys Gly Leu Glu Asn Asp Lys His Trp Val Gly
355 360 365
Cys Cys Tyr Ser Ser Val Asn Asp Arg Leu Val Ser Leu Gln Ser Thr
370 375 380
Lys Glu Glu Phe Met Arg Leu Leu Lys Asn Arg Arg Lys Ser Arg Val
385 390 395 400
His Lys Lys Ala Ser Leu Asp Glu Leu Phe Arg Val Ser Ile Asn Glu
405 410 415
Phe Ile Ala Lys Ile Gln Lys Cys Leu Ser Thr Val Gly Leu Ser Phe
420 425 430
Glu His Tyr Gly Leu Ser Glu Cys Leu Val Gln Glu Cys His Ile Pro
435 440 445
Phe Ala Glu Phe Glu Asn Phe Met Arg Ala Gly Thr His Pro Val Met
450 455 460
His Tyr Thr Lys Phe Glu Asp Tyr Thr Phe Gln Pro Asn Ile Glu Gln
465 470 475 480
Leu Arg Gly Leu Gln Ser Leu Arg Lys Leu Ser Ser Val Cys Leu Ala
485 490 495
Leu Thr Asn Ser Met Lys Thr Ser Ser Val Ala Arg Leu Arg Gln Asn
500 505 510
Gln Leu Gly Ser Val Arg Tyr Gln Val Val Glu Cys Lys Glu Val Phe
515 520 525
Cys Gln Ile Ile Lys Leu Asp Ser Glu Glu Tyr His Leu Leu Tyr Gln
530 535 540
Lys Thr Gly Glu Ser Ser Arg Cys Tyr Ser Ile Gln Gly Pro Asp Gly
545 550 555 560
His Leu Ile Ser Phe Tyr Ala Asp Pro Lys Arg Phe Phe Leu Pro Ile
565 570 575
Phe Ser Asp Glu Val Leu His Asn Met Ile Asp Thr Met Ile Ser Trp
580 585 590
Ile Arg Ser Cys Pro Asp Leu Lys Asp Ser Leu Ile Asp Ile Glu Thr
595 600 605
Ala Leu Arg Thr Leu Ile Leu Leu Met Leu Thr Asn Pro Thr Lys Arg
610 615 620
Asn Gln Lys Gln Val Gln Asn Ile Arg Tyr Leu Val Met Ala Ile Val
625 630 635 640
Ser Asp Phe Ser Ser Thr Ser Leu Met Asp Lys Leu Lys Glu Asp Leu
645 650 655
Ile Thr Pro Ala Glu Lys Val Val Tyr Arg Leu Leu Arg Phe Leu Ile
660 665 670
Arg Thr Ile Phe Gly Thr Gly Glu Lys Val Leu Leu Ser Ala Lys Phe
675 680 685
Lys Phe Met Leu Asn Val Ser Tyr Leu Cys His Leu Ile Thr Lys Glu
690 695 700
Thr Pro Asp Arg Leu Thr Asp Gln Ile Lys Cys Phe Glu Lys Phe Phe
705 710 715 720
Glu Pro Lys Ser Glu Phe Gly Phe Phe Val Asn Pro Lys Glu Thr Ile
725 730 735
Thr Pro Glu Glu Glu Cys Val Phe Tyr Glu Gln Met Lys Lys Phe Thr
740 745 750
Gly Lys Asp Ile Asp Cys Gln His Ser Thr Pro Gly Val Asn Leu Glu
755 760 765
Ile Phe Ser Met Met Val Ser Ser Phe Asn Asn Gly Thr Leu Ile Leu
770 775 780
Lys Gly Glu Lys Arg Leu Asn Asn Leu Asp Pro Met Thr Asn Ser Gly
785 790 795 800
Cys Ala Thr Ala Leu Asp Leu Ala Ser Asn Lys Ser Val Val Val Asn
805 810 815
Lys His Leu Asn Gly Glu Arg Leu Leu Glu Tyr Asp Phe Asn Lys Leu
820 825 830
Leu Val Ser Ala Val Ser Gln Ile Thr Glu Gly Phe Met Arg Lys Gln
835 840 845
Lys Tyr Lys Leu Arg His Ser Asp Tyr Glu Tyr Lys Val Ser Lys Leu
850 855 860
Val Ser Arg Leu Val Ile Gly Ser Arg Lys Thr Glu Val Asp Lys Leu
865 870 875 880
Glu Asp Asp Pro Val Asp Val Cys Phe Glu Gly Glu Glu Glu Thr Ser
885 890 895
Phe Phe Arg Ser Leu Glu Asp Lys Val Ser Ser Thr Ile Thr Arg Tyr
900 905 910
Asn Arg Gly Thr Arg Leu Asn Glu Gly Gln Gly Glu Gly Glu Phe Lys
915 920 925
Asn Thr Lys Gly Leu His His Leu Gln Ile Ile Leu Ser Gly Lys Arg
930 935 940
Ala Tyr Leu Arg Lys Val Ile Leu Ser Glu Ile Ser Phe His Leu Val
945 950 955 960
Glu Asp Phe Asp Pro Ser Cys Leu Thr Asn Asp Asp Met Arg Phe Ile
965 970 975
Cys Glu Ala Val Glu Gly Ser Thr Glu Leu Ser Pro Leu Tyr Phe Thr
980 985 990
Ser Ala Val Lys Glu Gln Cys Gly Leu Asp Glu Met Ala Arg Asn Leu
995 1000 1005
Cys Arg Lys Phe Phe Ser Glu Gly Asp Trp Phe Ser Cys Met Lys
1010 1015 1020
Met Ile Leu Leu Gln Met Asn Ala Asn Ala Tyr Ser Gly Lys Tyr
1025 1030 1035
Arg His Met Gln Arg Gln Ser Leu Asn Phe Lys Phe Asp Trp Asp
1040 1045 1050
Lys Leu Glu Glu Asp Val Arg Ile Ser Glu Arg Glu Ser Asn Ser
1055 1060 1065
Glu Ser Leu Ser Lys Ala Leu Ser Leu Thr Lys Cys Met Ser Ala
1070 1075 1080
Ala Leu Lys Asn Leu Cys Phe Tyr Ser Glu Glu Ser Pro Thr Ser
1085 1090 1095
Tyr Thr Ser Val Gly Pro Asp Ser Gly Arg Leu Lys Phe Ala Leu
1100 1105 1110
Ser Tyr Lys Glu Gln Val Gly Gly Asn Arg Glu Leu Tyr Ile Gly
1115 1120 1125
Asp Leu Arg Thr Lys Met Phe Thr Arg Leu Val Glu Asp Tyr Phe
1130 1135 1140
Glu Ser Phe Ser Ser Phe Phe Ser Gly Ser Cys Leu Asn Asn Asp
1145 1150 1155
Lys Glu Phe Glu Asn Ala Ile Leu Ser Met Thr Ile Asn Val Arg
1160 1165 1170
Glu Gly Leu Leu Asn Tyr Ser Met Asp His Ser Lys Trp Gly Pro
1175 1180 1185
Met Met Cys Pro Phe Leu Phe Leu Met Leu Leu Gln Asn Leu Lys
1190 1195 1200
Leu Gly Asp Asp Gln Tyr Val Arg Ser Gly Lys Asp His Val Ser
1205 1210 1215
Thr Leu Leu Thr Trp His Met His Lys Leu Val Glu Val Pro Phe
1220 1225 1230
Pro Val Val Asn Ala Met Met Lys Ser Tyr Val Lys Ser Lys Leu
1235 1240 1245
Lys Leu Leu Lys Gly Ser Gly Thr Thr Val Thr Glu Arg Ile Phe
1250 1255 1260
Arg Glu Tyr Phe Glu Met Gly Val Val Pro Ser His Ile Ser Ser
1265 1270 1275
Leu Ile Asp Met Gly Gln Gly Ile Leu His Asn Ala Ser Asp Phe
1280 1285 1290
Tyr Gly Leu Ile Ser Glu Arg Phe Ile Asn Tyr Cys Ile Gly Val
1295 1300 1305
Ile Phe Gly Glu Arg Pro Glu Ala Tyr Thr Ser Ser Asp Asp Gln
1310 1315 1320
Ile Thr Leu Phe Asp Lys Arg Leu Ser Asp Leu Val Asp Ser Asp
1325 1330 1335
Pro Glu Glu Val Leu Val Leu Leu Glu Phe His Ser His Leu Ser
1340 1345 1350
Gly Leu Leu Asn Lys Phe Ile Ser Pro Lys Ser Val Val Gly Arg
1355 1360 1365
Phe Ala Ala Glu Phe Lys Ser Arg Phe Tyr Val Trp Gly Glu Glu
1370 1375 1380
Val Pro Leu Leu Thr Lys Phe Val Ser Ala Ala Leu His Asn Val
1385 1390 1395
Lys Cys Lys Glu Pro His Gln Leu Cys Glu Thr Ile Asp Thr Ile
1400 1405 1410
Ala Asp Gln Ala Ile Ala Asn Gly Val Pro Val Phe Leu Val Asn
1415 1420 1425
Cys Ile Gln Arg Arg Thr Leu Asp Leu Leu Lys Tyr Ala Asn Phe
1430 1435 1440
Pro Leu Asp Pro Phe Leu Leu Asn Thr His Thr Asp Val Lys Asp
1445 1450 1455
Trp Leu Asp Gly Ser Arg Gly Tyr Arg Ile Gln Arg Leu Ile Glu
1460 1465 1470
Glu Leu Cys Pro Ser Glu Thr Lys Ile Met Arg Lys Leu Val Arg
1475 1480 1485
Arg Leu His His Lys Leu Lys Asn Gly Glu Cys Asn Glu Glu Phe
1490 1495 1500
Phe Leu Asp Leu Phe Asn Arg Glu Lys Lys Glu Ala Ile Leu Gln
1505 1510 1515
Leu Gly Glu Ile Leu Gly Leu Glu Asp Asp Leu Asn Glu Leu Ala
1520 1525 1530
Ser Ile Asn Trp Leu Asn Leu Asn Glu Met Phe Pro Leu Arg Met
1535 1540 1545
Val Leu Arg Gln Lys Val Val Tyr Pro Ser Val Met Thr Phe Gln
1550 1555 1560
Glu Glu Lys Ile Pro Ser Leu Ile Lys Thr Leu Gln Asn Lys Leu
1565 1570 1575
Cys Ser Lys Phe Thr Arg Gly Ala Gln Lys Leu Leu Ser Glu Ala
1580 1585 1590
Ile Asn Lys Ser Ala Phe Gln Ser Cys Val Ser Ser Gly Phe Ile
1595 1600 1605
Gly Leu Cys Lys Thr Leu Gly Ser Arg Cys Val Arg Asn Lys Asn
1610 1615 1620
Arg Glu Asn Met Tyr Ile Arg Lys Val Leu Glu Asp Leu Thr Met
1625 1630 1635
Asp Glu His Val Thr Arg Val His Lys Gln Asp Gly Val Met Leu
1640 1645 1650
Tyr Ile Cys Asp Lys Gln Arg His Pro Glu Ala His Arg Asp His
1655 1660 1665
Ile Asn Leu Leu Arg Pro Leu Leu Trp Asp Tyr Ile Cys Ile Ser
1670 1675 1680
Leu Ser Asn Ser Phe Glu Leu Gly Val Trp Val Leu Ala Glu Pro
1685 1690 1695
Val Lys Gly Lys Asn Glu Ser Asn Ser Ala Val Arg His Leu Asn
1700 1705 1710
Pro Cys Asp Tyr Val Ala Arg Lys Pro Glu Ser Ser Arg Leu Leu
1715 1720 1725
Glu Asp Lys Val Ser Leu Asn His Val Ile Gln Ser Val Arg Arg
1730 1735 1740
Leu Tyr Pro Lys Ile Phe Glu Asp Gln Leu Leu Pro Phe Met Phe
1745 1750 1755
Asp Val Ser Ser Lys Asn Met Arg Trp Ser Pro Arg Ile Lys Phe
1760 1765 1770
Leu Asp Leu Cys Val Leu Ile Asp Ile Asn Ser Glu Ser Leu Ser
1775 1780 1785
Leu Ile Ser His Val Val Lys Trp Lys Arg Asp Glu His Tyr Thr
1790 1795 1800
Val Leu Phe Ser Asp Leu Val Asn Ser His Gln Arg Ser Asp Ser
1805 1810 1815
Ser Leu Val Asp Glu Phe Val Val Ser Thr Arg Asp Val Cys Lys
1820 1825 1830
Asn Phe Leu Lys Gln Val Tyr Phe Glu Ser Phe Val Arg Glu Phe
1835 1840 1845
Val Ala Thr Ala Arg Thr Leu Gly Asn Phe Ser Trp Phe Pro His
1850 1855 1860
Lys Asp Met Met Pro Ser Glu Asp Gly Ala Glu Ala Leu Gly Pro
1865 1870 1875
Phe Gln Ser Phe Ile Leu Lys Val Val Asn Lys Lys Ile Glu Arg
1880 1885 1890
Pro Met Phe Arg Asn Asp Leu Gln Phe Gly Phe Gly Trp Phe Ser
1895 1900 1905
Tyr Arg Val Gly Asp Val Val Cys Asn Ala Ala Met Leu Ile Lys
1910 1915 1920
Gln Gly Leu Thr Asp Pro Lys Ala Phe Lys Ser Leu Arg Asp Leu
1925 1930 1935
Trp Asp Tyr Met Leu Ser Ser Thr Glu Gly Ile Leu Glu Phe Ser
1940 1945 1950
Ile Thr Val Asp Phe Thr His Asn Gln Asn Asn Thr Asp Cys Leu
1955 1960 1965
Arg Lys Phe Ser Leu Ile Phe Val Val Lys Cys Gln Leu Gln Ser
1970 1975 1980
Pro Gly Val Ala Asp Tyr Leu Ser Cys Ser His Phe Phe Lys Gly
1985 1990 1995
Glu Val Asp Arg Arg Leu Leu Asp Glu Cys Leu Asn Leu Leu Arg
2000 2005 2010
Thr Asp Pro Ile Phe Lys Ala Asn Asp Gly Val Phe Asp Ile Arg
2015 2020 2025
Ser Glu Glu Phe Glu Asp Tyr Met Glu Asp Pro Leu Thr Leu Gly
2030 2035 2040
Asp Ser Leu Glu Leu Glu Leu Ile Gly Ser Arg Arg Ile Leu Asn
2045 2050 2055
Glu Ile Lys Ser Thr Asp Phe Glu Arg Ile Gly Pro Glu Trp Glu
2060 2065 2070
Pro Val Pro Leu Thr Ile Arg Lys Gly Ala Leu Phe Glu Gly Arg
2075 2080 2085
Asn Phe Val Gln Asn Ile Ser Val Lys Leu Glu Thr Lys Asp Met
2090 2095 2100
Arg Val Phe Leu Ala Glu Leu Glu Gly Cys Gly Lys Ile Gly Asp
2105 2110 2115
Val Leu Gly Ser Leu Leu Leu His Arg Phe Arg Thr Gly Glu His
2120 2125 2130
Leu Met Glu Ser Glu Ile Ser Thr Val Leu Gln Glu Leu Cys Met
2135 2140 2145
Asp Arg Ser Val Met Leu Thr Pro Leu Ser Phe Val Pro Asp Trp
2150 2155 2160
Phe Thr Phe Arg Asp Cys Arg Leu Cys Phe Ser Arg Ser Lys Asn
2165 2170 2175
Thr Val Met Tyr Glu Thr Thr Gly Gly Arg Phe Arg Leu Lys Gly
2180 2185 2190
Lys Ser Cys Asp Asp Trp Leu Ala Glu Arg Val Ala Glu Glu Ile
2195 2200 2205
Asp
<210> 25
<211> 1497
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52)
<400> 25
atgggtcaga ttgtgacaat gtttgaggct ttgcctcaca tcattgatga ggtcatcaac 60
attgtcatta ttgtgctcat tataatcacg agcatcaaag ctgtgtacaa tttcgccacc 120
tgtgggatat tagcactggt cagcttcctt tttttggctg gtaggtcctg tggcatgtac 180
ggccttaatg gtcccgacat ctataaaggg gtttaccagt tcaaatcagt ggagtttgat 240
atgtctcact taaatctgac gatgcccaat gcgtgctcag ccaacaactc tcatcactac 300
atcagtatgg gaagctctgg actggagcta actttcacta acgactccat ccttaatcac 360
aatttttgca acttaacctc cgctttcaac aaaaagactt ttgaccatac actcatgagt 420
atagtctcga gtctgcacct cagtattaga gggaattcca accacaaagc agtgtcttgt 480
gattttaaca atggcatcac cattcaatac aacttgtcat tttcggaccc acagagcgct 540
atgagccagt gttggacttt cagaggtaga gtcttggaca tgtttagaac tgcctttgga 600
ggaaaataca tgagaagtgg ctggggctgg gcaggttcag atggcaagac cacttggtgc 660
agccaaacaa gctatcagta cctaatcata caaaacagga cttgggaaaa ccactgtaga 720
tatgcaggcc cttttgggat gtctagaatc ctctttgctc aggaaaagac aaagtttctc 780
actaggagac ttgcaggcac attcacctgg accctgtcag actcctcagg agtagaaaat 840
ccaggtggtt attgcctgac caaatggatg atccttgctg cagagctcaa atgttttggg 900
aatacagctg ttgcaaaatg taatgtcaat catgatgaag agttctgtga catgctacga 960
ctaattgatt acaacaaggc cgccctgagt aagttcaagc aagatgtaga gtctgccttg 1020
catgtattca aaacaacagt aaattctctg atttccgatc agctgttgat gaggaatcat 1080
ctaagagatc taatgggggt accatactgt aattactcaa agttctggta tctggaacat 1140
gctaagactg gtgagactag tgtacccaag tgctggcttg tcactaatgg ctcctacttg 1200
aatgagaccc actttagtga tcaaatcgaa caagaagcag ataacatgat cacagagatg 1260
ttgaggaagg actacataaa aagacaaggg agtactcctt tagccttaat ggatcttttg 1320
atgttttcaa catcagcata tctaatcagc atctttctgc atcttgtgaa gataccaaca 1380
catagacaca taaagggcgg ttcatgtcca aagccacacc gcttgaccaa caaggggatc 1440
tgtagttgtg gtgcattcaa ggtgcctggt gtaaaaacta tctggaaaag acgctga 1497
<210> 26
<211> 498
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52)
<400> 26
Met Gly Gln Ile Val Thr Met Phe Glu Ala Leu Pro His Ile Ile Asp
1 5 10 15
Glu Val Ile Asn Ile Val Ile Ile Val Leu Ile Ile Ile Thr Ser Ile
20 25 30
Lys Ala Val Tyr Asn Phe Ala Thr Cys Gly Ile Leu Ala Leu Val Ser
35 40 45
Phe Leu Phe Leu Ala Gly Arg Ser Cys Gly Met Tyr Gly Leu Asn Gly
50 55 60
Pro Asp Ile Tyr Lys Gly Val Tyr Gln Phe Lys Ser Val Glu Phe Asp
65 70 75 80
Met Ser His Leu Asn Leu Thr Met Pro Asn Ala Cys Ser Ala Asn Asn
85 90 95
Ser His His Tyr Ile Ser Met Gly Ser Ser Gly Leu Glu Leu Thr Phe
100 105 110
Thr Asn Asp Ser Ile Leu Asn His Asn Phe Cys Asn Leu Thr Ser Ala
115 120 125
Phe Asn Lys Lys Thr Phe Asp His Thr Leu Met Ser Ile Val Ser Ser
130 135 140
Leu His Leu Ser Ile Arg Gly Asn Ser Asn His Lys Ala Val Ser Cys
145 150 155 160
Asp Phe Asn Asn Gly Ile Thr Ile Gln Tyr Asn Leu Ser Phe Ser Asp
165 170 175
Pro Gln Ser Ala Met Ser Gln Cys Trp Thr Phe Arg Gly Arg Val Leu
180 185 190
Asp Met Phe Arg Thr Ala Phe Gly Gly Lys Tyr Met Arg Ser Gly Trp
195 200 205
Gly Trp Ala Gly Ser Asp Gly Lys Thr Thr Trp Cys Ser Gln Thr Ser
210 215 220
Tyr Gln Tyr Leu Ile Ile Gln Asn Arg Thr Trp Glu Asn His Cys Arg
225 230 235 240
Tyr Ala Gly Pro Phe Gly Met Ser Arg Ile Leu Phe Ala Gln Glu Lys
245 250 255
Thr Lys Phe Leu Thr Arg Arg Leu Ala Gly Thr Phe Thr Trp Thr Leu
260 265 270
Ser Asp Ser Ser Gly Val Glu Asn Pro Gly Gly Tyr Cys Leu Thr Lys
275 280 285
Trp Met Ile Leu Ala Ala Glu Leu Lys Cys Phe Gly Asn Thr Ala Val
290 295 300
Ala Lys Cys Asn Val Asn His Asp Glu Glu Phe Cys Asp Met Leu Arg
305 310 315 320
Leu Ile Asp Tyr Asn Lys Ala Ala Leu Ser Lys Phe Lys Gln Asp Val
325 330 335
Glu Ser Ala Leu His Val Phe Lys Thr Thr Val Asn Ser Leu Ile Ser
340 345 350
Asp Gln Leu Leu Met Arg Asn His Leu Arg Asp Leu Met Gly Val Pro
355 360 365
Tyr Cys Asn Tyr Ser Lys Phe Trp Tyr Leu Glu His Ala Lys Thr Gly
370 375 380
Glu Thr Ser Val Pro Lys Cys Trp Leu Val Thr Asn Gly Ser Tyr Leu
385 390 395 400
Asn Glu Thr His Phe Ser Asp Gln Ile Glu Gln Glu Ala Asp Asn Met
405 410 415
Ile Thr Glu Met Leu Arg Lys Asp Tyr Ile Lys Arg Gln Gly Ser Thr
420 425 430
Pro Leu Ala Leu Met Asp Leu Leu Met Phe Ser Thr Ser Ala Tyr Leu
435 440 445
Ile Ser Ile Phe Leu His Leu Val Lys Ile Pro Thr His Arg His Ile
450 455 460
Lys Gly Gly Ser Cys Pro Lys Pro His Arg Leu Thr Asn Lys Gly Ile
465 470 475 480
Cys Ser Cys Gly Ala Phe Lys Val Pro Gly Val Lys Thr Ile Trp Lys
485 490 495
Arg Arg
<210> 27
<211> 1677
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52)
<400> 27
atgtctttgt ccaaagaagt caaaagcttt cagtggacac aggcgttgag gagggagttg 60
cagagtttta catcagatgt aaaggctgcc gtcatcaagg acgcaaccag tcttctaaat 120
gggttggact tttctgaagt cagcaacgtt cagaggatca tgagaaagga aaggagggat 180
gataaagact tgcagagact caggagtctt aaccagactg tgcattctct tgttgatctg 240
aagtctacat caaagaaaaa tgttctgaaa gtgggaagac ttagtgcaga ggaattgatg 300
acccttgcag ctgatcttga gaagctgaag gccaaaatta tgagaactga gaggcctcaa 360
gcttctggag tctacatggg aaatttgaca gcacaacaac ttgatcaaag atcccaaata 420
ctgcaaatgg ttgggatgag aagacctcag cagggtgcaa gtggtgtagt aagggtttgg 480
gatgtgaagg actcatcact tctgaacaat cagttcggca caatgccaag cctgacaatg 540
gcttgcatgg caaaacagtc acagacccca ctcaatgatg ttgtgcaggc actcacagac 600
cttggcttac tttacacagt caaatacccg aatctcagtg atcttgaaag gctaaaggat 660
aaacacccag ttctgggggt cattactgaa cagcaatcta gtatcaatat ctctggttat 720
aatttcagtc ttggtgcagc tgtgaaagcg ggggcagctc tgctagatgg agggaacatg 780
ctggaatcta tcttgatcaa accgagcaac agtgaggatc tcctaaaagc agtcctcggg 840
gccaagaaga aactcaacat gtttgtctca gatcaagttg gagatagaaa tccctatgaa 900
aacatccttt ataaagtctg tctttcaggt gaaggatggc catacatagc ctgtagaacg 960
tcagttgtgg ggagagcatg ggagaacaca acaattgatc tcacaaatga aaaacttgtt 1020
gccaactcat ctaggccagt gcctggagca gcaggcccac ctcaggtggg cttgagttac 1080
agtcagacaa tgctgttgaa agacttgatg ggagggattg atcccaatgc tcccacatgg 1140
attgacattg agggcaggtt caatgatcca gtggagatag caatattcca accacaaaat 1200
gggcaattca tacattttta cagggaacct acggaccaga agcaattcaa gcaggactca 1260
aagtattcac acggcatgga tcttgctgat ctcttcaatg cacagcctgg gctgacctca 1320
tcagttatag gtgctctccc acaagggatg gttttgagct gtcaaggttc tgatgacatc 1380
agaaagcttc tggactcaca aaayagaagg gacataaaac tcattgatgt tgagatgacc 1440
aaggaggcct caagagaata tgaagataaa gtgtgggaca aatatggctg gctatgcaaa 1500
atgcacactg gggtagtgag agacaaaaag aagaaagaga tcaccccaca ctgtgcactc 1560
atggactgca tcatttttga gagtgcttcc aaggcaagac tccctgatct aaaaaccgtt 1620
cacaacatcc tgccacatga tttaatcttc agaggaccca atgttgtgac actctaa 1677
<210> 28
<211> 558
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52)
<400> 28
Met Ser Leu Ser Lys Glu Val Lys Ser Phe Gln Trp Thr Gln Ala Leu
1 5 10 15
Arg Arg Glu Leu Gln Ser Phe Thr Ser Asp Val Lys Ala Ala Val Ile
20 25 30
Lys Asp Ala Thr Ser Leu Leu Asn Gly Leu Asp Phe Ser Glu Val Ser
35 40 45
Asn Val Gln Arg Ile Met Arg Lys Glu Arg Arg Asp Asp Lys Asp Leu
50 55 60
Gln Arg Leu Arg Ser Leu Asn Gln Thr Val His Ser Leu Val Asp Leu
65 70 75 80
Lys Ser Thr Ser Lys Lys Asn Val Leu Lys Val Gly Arg Leu Ser Ala
85 90 95
Glu Glu Leu Met Thr Leu Ala Ala Asp Leu Glu Lys Leu Lys Ala Lys
100 105 110
Ile Met Arg Thr Glu Arg Pro Gln Ala Ser Gly Val Tyr Met Gly Asn
115 120 125
Leu Thr Ala Gln Gln Leu Asp Gln Arg Ser Gln Ile Leu Gln Met Val
130 135 140
Gly Met Arg Arg Pro Gln Gln Gly Ala Ser Gly Val Val Arg Val Trp
145 150 155 160
Asp Val Lys Asp Ser Ser Leu Leu Asn Asn Gln Phe Gly Thr Met Pro
165 170 175
Ser Leu Thr Met Ala Cys Met Ala Lys Gln Ser Gln Thr Pro Leu Asn
180 185 190
Asp Val Val Gln Ala Leu Thr Asp Leu Gly Leu Leu Tyr Thr Val Lys
195 200 205
Tyr Pro Asn Leu Ser Asp Leu Glu Arg Leu Lys Asp Lys His Pro Val
210 215 220
Leu Gly Val Ile Thr Glu Gln Gln Ser Ser Ile Asn Ile Ser Gly Tyr
225 230 235 240
Asn Phe Ser Leu Gly Ala Ala Val Lys Ala Gly Ala Ala Leu Leu Asp
245 250 255
Gly Gly Asn Met Leu Glu Ser Ile Leu Ile Lys Pro Ser Asn Ser Glu
260 265 270
Asp Leu Leu Lys Ala Val Leu Gly Ala Lys Lys Lys Leu Asn Met Phe
275 280 285
Val Ser Asp Gln Val Gly Asp Arg Asn Pro Tyr Glu Asn Ile Leu Tyr
290 295 300
Lys Val Cys Leu Ser Gly Glu Gly Trp Pro Tyr Ile Ala Cys Arg Thr
305 310 315 320
Ser Val Val Gly Arg Ala Trp Glu Asn Thr Thr Ile Asp Leu Thr Asn
325 330 335
Glu Lys Leu Val Ala Asn Ser Ser Arg Pro Val Pro Gly Ala Ala Gly
340 345 350
Pro Pro Gln Val Gly Leu Ser Tyr Ser Gln Thr Met Leu Leu Lys Asp
355 360 365
Leu Met Gly Gly Ile Asp Pro Asn Ala Pro Thr Trp Ile Asp Ile Glu
370 375 380
Gly Arg Phe Asn Asp Pro Val Glu Ile Ala Ile Phe Gln Pro Gln Asn
385 390 395 400
Gly Gln Phe Ile His Phe Tyr Arg Glu Pro Thr Asp Gln Lys Gln Phe
405 410 415
Lys Gln Asp Ser Lys Tyr Ser His Gly Met Asp Leu Ala Asp Leu Phe
420 425 430
Asn Ala Gln Pro Gly Leu Thr Ser Ser Val Ile Gly Ala Leu Pro Gln
435 440 445
Gly Met Val Leu Ser Cys Gln Gly Ser Asp Asp Ile Arg Lys Leu Leu
450 455 460
Asp Ser Gln Asn Arg Arg Asp Ile Lys Leu Ile Asp Val Glu Met Thr
465 470 475 480
Lys Glu Ala Ser Arg Glu Tyr Glu Asp Lys Val Trp Asp Lys Tyr Gly
485 490 495
Trp Leu Cys Lys Met His Thr Gly Val Val Arg Asp Lys Lys Lys Lys
500 505 510
Glu Ile Thr Pro His Cys Ala Leu Met Asp Cys Ile Ile Phe Glu Ser
515 520 525
Ala Ser Lys Ala Arg Leu Pro Asp Leu Lys Thr Val His Asn Ile Leu
530 535 540
Pro His Asp Leu Ile Phe Arg Gly Pro Asn Val Val Thr Leu
545 550 555
<210> 29
<211> 273
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52)
<400> 29
atgggccaag gcaagtccaa agaagaaagg gacaccagca atacaggcag agcagagctt 60
ttgccagaca ccacctatct tggtcctcta aattgtaaat catgttggca gaaatttgac 120
agcttggtta gatgccatga ccactatctt tgcagacact gtctgaatct cctgctgtca 180
gtttccgaca gatgtcctct ctgtaagtat ccactgccaa ccaaactgaa ggtgtcaaca 240
gtcccaagct ccccacctcc ctatgaggag tga 273
<210> 30
<211> 90
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52)
<400> 30
Met Gly Gln Gly Lys Ser Lys Glu Glu Arg Asp Thr Ser Asn Thr Gly
1 5 10 15
Arg Ala Glu Leu Leu Pro Asp Thr Thr Tyr Leu Gly Pro Leu Asn Cys
20 25 30
Lys Ser Cys Trp Gln Lys Phe Asp Ser Leu Val Arg Cys His Asp His
35 40 45
Tyr Leu Cys Arg His Cys Leu Asn Leu Leu Leu Ser Val Ser Asp Arg
50 55 60
Cys Pro Leu Cys Lys Tyr Pro Leu Pro Thr Lys Leu Lys Val Ser Thr
65 70 75 80
Val Pro Ser Ser Pro Pro Pro Tyr Glu Glu
85 90
<210> 31
<211> 6630
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52)
<400> 31
atggatgaaa ctattgcaga tttgagagag ttgtgtctaa attacataga acaggacgag 60
aggctgtcaa ggcaaaaact caacttcctg ggacaaagag aacccagaat ggtgctaatt 120
gagggactca aattgttatc acgctgtata gagatagaca gtgcagacaa aagtggttgc 180
atacacaacc acgatgacaa atctgttgaa acaatcctaa tagactctgg gattgtgtgt 240
ccaggactgc cactcatcat ccctgatggt tataagttga ttgacaattc ccttattctt 300
cttgaatgtt ttgttagaag cacaccagct agttttgaaa agaagttcat tgaggacacc 360
aacaaactag catgcatcaa agaagatctt gctgttgcag gcatcacact ggttccaata 420
gtggatggtc gttgtgatta tgataacagt ttcatgccag aatgggtgaa ttttaagttc 480
agagacctcc tatttaaact cctggagtat tctagtcaag atgagaaagt ttttgaggag 540
tctgaatact tcaggctctg tgagtctctt aagaccactg ttgacaaacg ttccggcatg 600
gactcaatga aaattttgaa agacgcaaga tcatttcata acgatgagat tatgaaaatg 660
tgccacgatg gtgtcaaccc caacatgagt tgcgatgatg tggtctttgg cataaattcc 720
ttttttggca ggtttaggag ggacctgtta aatgggaaac tcaaaaggaa tttccaaaag 780
gtcagccctg ggggcttaat caaggaattc tctgaacttt atgaaaccct tactgataat 840
gatgacatat taatgttgag caaagaggca gttgaatcct gccccttaat gaggttcatt 900
acagcagaga cccatgggca tgagagagga agcgatgcta acactgagta tgaaaggcta 960
ctctctatgt tgaacaaggt gaaaagttta aaattattaa acactagaag gagacagctg 1020
ctgaacttag atgtcttatg tctttcttca cttattaagc agtcaatttc caaagggttg 1080
gaaaatgata aacattgggt tggttgttgc tacagtagtg tgaatgatag gcttgtgagc 1140
cttcaaagta ccaaagaaga attcatgaga cttttgaaga acagaagaaa atcaagagtg 1200
cacaaaaagg catctcttga tgagcttttt agggtatcca taaatgagtt catagcaaaa 1260
atccagaaat gcctatcaac agtgggactt agttttgagc attacggact atcagaatgc 1320
ctcgtgcaag aatgccatat accatttgct gaatttgaga actttatgag agccgggact 1380
catcctgtaa tgcattacac aaaatttgaa gattacactt tccagcctaa catagagcaa 1440
ttgaggggtt tacagagttt gagaaaactg tcatctgttt gtttggctct aacaaacagc 1500
atgaaaacaa gctcagttgc aaggttgaga cagaaccaac tggggtctgt gagatatcaa 1560
gtggtggagt gcaaagaggt gttttgccag ataataaaac tggattccga agagtatcat 1620
ctactatatc agaaaactgg agaatcatcg aggtgttatt ccatacaagg tccggatggt 1680
cacttgattt ccttttacgc agatccaaaa aggttctttt taccaatttt ttcagatgag 1740
gtgttgcaca acatgataga cacaatgatt tcatggatta ggtcatgccc tgacttaaaa 1800
gattctctta ttgacattga gactgcacta aggacattga tcctactgat gctcaccaac 1860
ccaacaaaga gaaatcaaaa gcaggttcaa aatattaggt atttagtgat ggccatcgtc 1920
tcagactttt catcgacctc attaatggat aagttgaagg aggatctaat cacacctgcc 1980
gagaaagtgg tgtacaggct gcttcggttt ttgattagga caatttttgg tactggtgaa 2040
aaggtgttat tgagtgcaaa attcaagttt atgttgaatg trtcatacct gtgtcatttg 2100
atcacaaagg agacccctga tagattgaca gatcagataa aatgttttga aaagttcttt 2160
gagcccaaga gtgagtttgg tttctttgtc aaccctaagg aaacaatcac acccgaagag 2220
gaatgtgttt tttatgaaca aatgaagaag ttcaccggta aagatattga ttgtcagcat 2280
tcaacccctg gtgttaattt agagatcttt agcatgatgg tatcttcatt caacaatggc 2340
accttaattc taaaagggga gaaaaggctc aacaatctgg accccatgac caactctgga 2400
tgtgcgacag cattagatct cgcaagcaac aaaagtgtgg ttgtcaataa acatctgaat 2460
ggagaacggc ttttggagta tgattttaac aaattgcttg ttagtgctgt gagccaaatt 2520
acagagggct tcatgaggaa acaaaagtat aagctgagac actcagatta cgaatataag 2580
gtctcaaagc ttgtctctag attagtcatc ggttccagga aaacagaagt agacaaattg 2640
gaagatgatc cggtagatgt gtgtttcgag ggggaggagg agacaagttt tttcaggagt 2700
ttagaagata aggtcagctc cacaataaca cggtataata gaggcactag gcttaatgaa 2760
gggcaagggg agggagaatt caagaacaca aaaggactac accaccttca gattattttg 2820
tcaggtaaaa gagcttatct gaggaaagtc attttatcag aaatttcatt tcatctagta 2880
gaggactttg atccatcctg tctcaccaat gacgacatga ggtttatttg tgaggctgtt 2940
gaaggttcaa cagaactgtc accattgtat tttacatcag ctgtcaaaga acaatgtggt 3000
ctggatgaga tggcaagaaa cctctgtaga aagttcttct cagagggtga ttggttctca 3060
tgtatgaaga tgatcttgtt acagatgaat gcaaatgcgt attcagggaa gtacagacac 3120
atgcagaggc agagcttaaa ttttaaattt gactgggaca aattggaaga agatgtaaga 3180
attagtgaaa gggaaagcaa ttctgaatct ctaagtaagg ccctttcatt gacaaaatgc 3240
atgagtgctg ctctaaagaa tctgtgtttt tactcagaag aatcaccaac atcatacact 3300
tcagttggcc ctgactctgg gagactaaaa tttgcattgt catacaaaga gcaggttggg 3360
ggaaatagag agctttacat tggggatttg aggacaaaaa tgttcacaag attggtagaa 3420
gattattttg aatccttttc tagtttcttt tcaggatctt gtttaaacaa tgacaaagag 3480
tttgaaaatg caatcttgtc aatgactatc aatgtgagag aagggttgtt aaactacagc 3540
atggatcaca gcaaatgggg accaatgatg tgcccattcc tattcttaat gcttctccaa 3600
aatctcaaac tgggtgatga tcagtacgtg cgttctggaa aagatcatgt tagcaccttg 3660
ttgacttggc atatgcataa acttgttgaa gtccctttcc ctgttgtgaa tgcaatgatg 3720
aaatcatatg ttaaatcaaa actcaagctt ctcaaagggt caggaacgac tgttacggag 3780
agaatcttta gagagtattt tgaaatgggg gtggtgccat ctcacatatc tagtctcatt 3840
gacatgggac aggggatcct acacaatgct tctgattttt acggtttaat tagtgaaagg 3900
tttatcaatt attgtattgg tgtcattttt ggagagaggc cagaagccta tacatcaagt 3960
gatgatcaga tcactttatt tgacaagaga ttgagtgact tagttgatag tgacccagaa 4020
gaagtccttg tcttgctgga attccactct cacttaagtg gtttgttgaa caagttcatc 4080
agtccaaaaa gtgtggttgg gcggtttgca gcggaattca aatccagatt ttatgtgtgg 4140
ggggaggagg tccctctcct cacgaaattt gtgtctgcgg cactacacaa tgttaagtgt 4200
aaagaaccgc atcaactttg tgagacaata gatacgattg ctgatcaagc tatagcaaat 4260
ggagttccag tttttttagt aaactgtatc cagaggagga cactggatct cttgaaatat 4320
gctaatttcc ctttagatcc attcttgtta aacactcaca ctgatgtaaa ggattggtta 4380
gatggttcta gaggttatag aatccaaaga ctcattgaag aattgtgtcc cagtgaaaca 4440
aagatcatga gaaaacttgt aagaagacta catcacaaac tcaagaacgg tgaatgtaac 4500
gaggaatttt ttctagacct cttcaacagg gaaaagaaag aggccatcct tcaattggga 4560
gagattcttg gtcttgagga tgatcttaat gagttggcaa gcatcaattg gttgaatctg 4620
aatgaaatgt tcccattgag gatggttctg agacaaaaag tggtttaccc atcagtaatg 4680
acctttcaag aggaaaagat cccctcattg attaaaacac tccaaaataa gctttgtagt 4740
aagttcacaa gaggtgcaca gaagctgttg tcagaggcaa tcaacaaatc agcttttcag 4800
agttgtgtct catccggctt tataggtctc tgtaagactt taggaagtag gtgtgtgaga 4860
aataaaaaca gggaaaatat gtatatcaga aaggtgcttg aagatctgac catggatgaa 4920
catgtcacaa gggttcacaa acaagatggt gtgatgttgt acatttgcga caagcagaga 4980
cacccagagg ctcaccgtga ccacatcaac cttttgaggc cccttctctg ggactacatt 5040
tgcatctcat tgagcaactc ttttgagctg ggtgtttggg ttttagcaga acctgtgaaa 5100
ggaaagaacg agagtaattc ggctgttagg cacttaaatc catgtgatta tgtagcaaga 5160
aaacctgaga gttcgagact actagaggat aaagtgagtt tgaatcatgt aattcaatct 5220
gtgaggcgac tgtaccccaa aatctttgag gatcagttgc tcccattcat gtctgatgtg 5280
agctcaaaaa atatgagatg gagtcccagg attaaattcc ttgacctttg tgtgctgatt 5340
gacatcaact cagagtcttt gtcactcatt tctcatgttg tcaaatggaa gagggacgaa 5400
cattacactg tgctgttttc tgatctcgtc aactctcacc aacggtcaga ctcaagttta 5460
gttgatgaat ttgttgtcag cacaagggat gtctgcaaga actttttgaa gcaagtgtat 5520
ttcgaatcat ttgtacgaga gtttgttgca acagctagga ccttaggtaa cttttcatgg 5580
ttcccccata aggacatgat gccatctgaa gatggcgctg aagcactggg acccttccaa 5640
tcatttattt tgaaagtggt gaacaagaaa atagagaggc ccatgtttag gaatgacttg 5700
cagtttggtt ttggttggtt ctcttatcgt gtgggggatg ttgtgtgtaa tgccgctatg 5760
ttaattaagc agggtttgac agatccaaaa gcatttaaat ctttaagaga tttgtgggat 5820
tacatgctca gcagcacaga ggggatattg gagttctcaa tcacagtgga tttcacacac 5880
aaccagaaca acactgactg cttgaggaaa ttttcattga tctttgtggt taaatgccaa 5940
ttacagagtc caggtgtagc tgattactta tcgtgctctc attccttcaa aggtgaggtt 6000
gacaggagat tattagatga gtgtctcaat ctgttgagga cagaccccat ctttaaagcg 6060
aatgatggag tctttgacat taggtctgaa gagtttgaag attacatgga agaccctttg 6120
acacttggtg attcactaga acttgaacta ataggttcta gaaggattct gaatgagatc 6180
aaatctactg actttgagag gatagggcct gagtgggaac ctgtgcctct gaccataagg 6240
aagggtgccc tctttgaggg gaggaacttt gttcagaatr tctctgtgaa attggagaca 6300
aaggacatga gggtctttct ggcagagctc gagggctgtg gaaaaattgg tgatgtcctc 6360
ggcagcctcc tcctgcaccg attcagaact ggtgagcact tgatggagtc agaaataagt 6420
rcagttcttc aggagctctg catggacaga tccgtcatgc tgacaccatt atcttttgtg 6480
ccagattggt tcaccttcag agattgtagg ctctgcttca gcaggtcaaa gaacactgta 6540
atgtatgaga caactggggg caggttcaga ctcaagggga aatcctgtga cgattggctg 6600
gcggagcggg tggccgagga gatcgactag 6630
<210> 32
<211> 2209
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52)
<220>
<221> MISC_FEATURE
<222> (2094)..(2094)
<223> Xaa可以是Ile或Val
<220>
<221> MISC_FEATURE
<222> (2141)..(2141)
<223> Xaa可以是Thr或Ala
<400> 32
Met Asp Glu Thr Ile Ala Asp Leu Arg Glu Leu Cys Leu Asn Tyr Ile
1 5 10 15
Glu Gln Asp Glu Arg Leu Ser Arg Gln Lys Leu Asn Phe Leu Gly Gln
20 25 30
Arg Glu Pro Arg Met Val Leu Ile Glu Gly Leu Lys Leu Leu Ser Arg
35 40 45
Cys Ile Glu Ile Asp Ser Ala Asp Lys Ser Gly Cys Ile His Asn His
50 55 60
Asp Asp Lys Ser Val Glu Thr Ile Leu Ile Asp Ser Gly Ile Val Cys
65 70 75 80
Pro Gly Leu Pro Leu Ile Ile Pro Asp Gly Tyr Lys Leu Ile Asp Asn
85 90 95
Ser Leu Ile Leu Leu Glu Cys Phe Val Arg Ser Thr Pro Ala Ser Phe
100 105 110
Glu Lys Lys Phe Ile Glu Asp Thr Asn Lys Leu Ala Cys Ile Lys Glu
115 120 125
Asp Leu Ala Val Ala Gly Ile Thr Leu Val Pro Ile Val Asp Gly Arg
130 135 140
Cys Asp Tyr Asp Asn Ser Phe Met Pro Glu Trp Val Asn Phe Lys Phe
145 150 155 160
Arg Asp Leu Leu Phe Lys Leu Leu Glu Tyr Ser Ser Gln Asp Glu Lys
165 170 175
Val Phe Glu Glu Ser Glu Tyr Phe Arg Leu Cys Glu Ser Leu Lys Thr
180 185 190
Thr Val Asp Lys Arg Ser Gly Met Asp Ser Met Lys Ile Leu Lys Asp
195 200 205
Ala Arg Ser Phe His Asn Asp Glu Ile Met Lys Met Cys His Asp Gly
210 215 220
Val Asn Pro Asn Met Ser Cys Asp Asp Val Val Phe Gly Ile Asn Ser
225 230 235 240
Phe Phe Gly Arg Phe Arg Arg Asp Leu Leu Asn Gly Lys Leu Lys Arg
245 250 255
Asn Phe Gln Lys Val Ser Pro Gly Gly Leu Ile Lys Glu Phe Ser Glu
260 265 270
Leu Tyr Glu Thr Leu Thr Asp Asn Asp Asp Ile Leu Met Leu Ser Lys
275 280 285
Glu Ala Val Glu Ser Cys Pro Leu Met Arg Phe Ile Thr Ala Glu Thr
290 295 300
His Gly His Glu Arg Gly Ser Asp Ala Asn Thr Glu Tyr Glu Arg Leu
305 310 315 320
Leu Ser Met Leu Asn Lys Val Lys Ser Leu Lys Leu Leu Asn Thr Arg
325 330 335
Arg Arg Gln Leu Leu Asn Leu Asp Val Leu Cys Leu Ser Ser Leu Ile
340 345 350
Lys Gln Ser Ile Ser Lys Gly Leu Glu Asn Asp Lys His Trp Val Gly
355 360 365
Cys Cys Tyr Ser Ser Val Asn Asp Arg Leu Val Ser Leu Gln Ser Thr
370 375 380
Lys Glu Glu Phe Met Arg Leu Leu Lys Asn Arg Arg Lys Ser Arg Val
385 390 395 400
His Lys Lys Ala Ser Leu Asp Glu Leu Phe Arg Val Ser Ile Asn Glu
405 410 415
Phe Ile Ala Lys Ile Gln Lys Cys Leu Ser Thr Val Gly Leu Ser Phe
420 425 430
Glu His Tyr Gly Leu Ser Glu Cys Leu Val Gln Glu Cys His Ile Pro
435 440 445
Phe Ala Glu Phe Glu Asn Phe Met Arg Ala Gly Thr His Pro Val Met
450 455 460
His Tyr Thr Lys Phe Glu Asp Tyr Thr Phe Gln Pro Asn Ile Glu Gln
465 470 475 480
Leu Arg Gly Leu Gln Ser Leu Arg Lys Leu Ser Ser Val Cys Leu Ala
485 490 495
Leu Thr Asn Ser Met Lys Thr Ser Ser Val Ala Arg Leu Arg Gln Asn
500 505 510
Gln Leu Gly Ser Val Arg Tyr Gln Val Val Glu Cys Lys Glu Val Phe
515 520 525
Cys Gln Ile Ile Lys Leu Asp Ser Glu Glu Tyr His Leu Leu Tyr Gln
530 535 540
Lys Thr Gly Glu Ser Ser Arg Cys Tyr Ser Ile Gln Gly Pro Asp Gly
545 550 555 560
His Leu Ile Ser Phe Tyr Ala Asp Pro Lys Arg Phe Phe Leu Pro Ile
565 570 575
Phe Ser Asp Glu Val Leu His Asn Met Ile Asp Thr Met Ile Ser Trp
580 585 590
Ile Arg Ser Cys Pro Asp Leu Lys Asp Ser Leu Ile Asp Ile Glu Thr
595 600 605
Ala Leu Arg Thr Leu Ile Leu Leu Met Leu Thr Asn Pro Thr Lys Arg
610 615 620
Asn Gln Lys Gln Val Gln Asn Ile Arg Tyr Leu Val Met Ala Ile Val
625 630 635 640
Ser Asp Phe Ser Ser Thr Ser Leu Met Asp Lys Leu Lys Glu Asp Leu
645 650 655
Ile Thr Pro Ala Glu Lys Val Val Tyr Arg Leu Leu Arg Phe Leu Ile
660 665 670
Arg Thr Ile Phe Gly Thr Gly Glu Lys Val Leu Leu Ser Ala Lys Phe
675 680 685
Lys Phe Met Leu Asn Val Ser Tyr Leu Cys His Leu Ile Thr Lys Glu
690 695 700
Thr Pro Asp Arg Leu Thr Asp Gln Ile Lys Cys Phe Glu Lys Phe Phe
705 710 715 720
Glu Pro Lys Ser Glu Phe Gly Phe Phe Val Asn Pro Lys Glu Thr Ile
725 730 735
Thr Pro Glu Glu Glu Cys Val Phe Tyr Glu Gln Met Lys Lys Phe Thr
740 745 750
Gly Lys Asp Ile Asp Cys Gln His Ser Thr Pro Gly Val Asn Leu Glu
755 760 765
Ile Phe Ser Met Met Val Ser Ser Phe Asn Asn Gly Thr Leu Ile Leu
770 775 780
Lys Gly Glu Lys Arg Leu Asn Asn Leu Asp Pro Met Thr Asn Ser Gly
785 790 795 800
Cys Ala Thr Ala Leu Asp Leu Ala Ser Asn Lys Ser Val Val Val Asn
805 810 815
Lys His Leu Asn Gly Glu Arg Leu Leu Glu Tyr Asp Phe Asn Lys Leu
820 825 830
Leu Val Ser Ala Val Ser Gln Ile Thr Glu Gly Phe Met Arg Lys Gln
835 840 845
Lys Tyr Lys Leu Arg His Ser Asp Tyr Glu Tyr Lys Val Ser Lys Leu
850 855 860
Val Ser Arg Leu Val Ile Gly Ser Arg Lys Thr Glu Val Asp Lys Leu
865 870 875 880
Glu Asp Asp Pro Val Asp Val Cys Phe Glu Gly Glu Glu Glu Thr Ser
885 890 895
Phe Phe Arg Ser Leu Glu Asp Lys Val Ser Ser Thr Ile Thr Arg Tyr
900 905 910
Asn Arg Gly Thr Arg Leu Asn Glu Gly Gln Gly Glu Gly Glu Phe Lys
915 920 925
Asn Thr Lys Gly Leu His His Leu Gln Ile Ile Leu Ser Gly Lys Arg
930 935 940
Ala Tyr Leu Arg Lys Val Ile Leu Ser Glu Ile Ser Phe His Leu Val
945 950 955 960
Glu Asp Phe Asp Pro Ser Cys Leu Thr Asn Asp Asp Met Arg Phe Ile
965 970 975
Cys Glu Ala Val Glu Gly Ser Thr Glu Leu Ser Pro Leu Tyr Phe Thr
980 985 990
Ser Ala Val Lys Glu Gln Cys Gly Leu Asp Glu Met Ala Arg Asn Leu
995 1000 1005
Cys Arg Lys Phe Phe Ser Glu Gly Asp Trp Phe Ser Cys Met Lys
1010 1015 1020
Met Ile Leu Leu Gln Met Asn Ala Asn Ala Tyr Ser Gly Lys Tyr
1025 1030 1035
Arg His Met Gln Arg Gln Ser Leu Asn Phe Lys Phe Asp Trp Asp
1040 1045 1050
Lys Leu Glu Glu Asp Val Arg Ile Ser Glu Arg Glu Ser Asn Ser
1055 1060 1065
Glu Ser Leu Ser Lys Ala Leu Ser Leu Thr Lys Cys Met Ser Ala
1070 1075 1080
Ala Leu Lys Asn Leu Cys Phe Tyr Ser Glu Glu Ser Pro Thr Ser
1085 1090 1095
Tyr Thr Ser Val Gly Pro Asp Ser Gly Arg Leu Lys Phe Ala Leu
1100 1105 1110
Ser Tyr Lys Glu Gln Val Gly Gly Asn Arg Glu Leu Tyr Ile Gly
1115 1120 1125
Asp Leu Arg Thr Lys Met Phe Thr Arg Leu Val Glu Asp Tyr Phe
1130 1135 1140
Glu Ser Phe Ser Ser Phe Phe Ser Gly Ser Cys Leu Asn Asn Asp
1145 1150 1155
Lys Glu Phe Glu Asn Ala Ile Leu Ser Met Thr Ile Asn Val Arg
1160 1165 1170
Glu Gly Leu Leu Asn Tyr Ser Met Asp His Ser Lys Trp Gly Pro
1175 1180 1185
Met Met Cys Pro Phe Leu Phe Leu Met Leu Leu Gln Asn Leu Lys
1190 1195 1200
Leu Gly Asp Asp Gln Tyr Val Arg Ser Gly Lys Asp His Val Ser
1205 1210 1215
Thr Leu Leu Thr Trp His Met His Lys Leu Val Glu Val Pro Phe
1220 1225 1230
Pro Val Val Asn Ala Met Met Lys Ser Tyr Val Lys Ser Lys Leu
1235 1240 1245
Lys Leu Leu Lys Gly Ser Gly Thr Thr Val Thr Glu Arg Ile Phe
1250 1255 1260
Arg Glu Tyr Phe Glu Met Gly Val Val Pro Ser His Ile Ser Ser
1265 1270 1275
Leu Ile Asp Met Gly Gln Gly Ile Leu His Asn Ala Ser Asp Phe
1280 1285 1290
Tyr Gly Leu Ile Ser Glu Arg Phe Ile Asn Tyr Cys Ile Gly Val
1295 1300 1305
Ile Phe Gly Glu Arg Pro Glu Ala Tyr Thr Ser Ser Asp Asp Gln
1310 1315 1320
Ile Thr Leu Phe Asp Lys Arg Leu Ser Asp Leu Val Asp Ser Asp
1325 1330 1335
Pro Glu Glu Val Leu Val Leu Leu Glu Phe His Ser His Leu Ser
1340 1345 1350
Gly Leu Leu Asn Lys Phe Ile Ser Pro Lys Ser Val Val Gly Arg
1355 1360 1365
Phe Ala Ala Glu Phe Lys Ser Arg Phe Tyr Val Trp Gly Glu Glu
1370 1375 1380
Val Pro Leu Leu Thr Lys Phe Val Ser Ala Ala Leu His Asn Val
1385 1390 1395
Lys Cys Lys Glu Pro His Gln Leu Cys Glu Thr Ile Asp Thr Ile
1400 1405 1410
Ala Asp Gln Ala Ile Ala Asn Gly Val Pro Val Phe Leu Val Asn
1415 1420 1425
Cys Ile Gln Arg Arg Thr Leu Asp Leu Leu Lys Tyr Ala Asn Phe
1430 1435 1440
Pro Leu Asp Pro Phe Leu Leu Asn Thr His Thr Asp Val Lys Asp
1445 1450 1455
Trp Leu Asp Gly Ser Arg Gly Tyr Arg Ile Gln Arg Leu Ile Glu
1460 1465 1470
Glu Leu Cys Pro Ser Glu Thr Lys Ile Met Arg Lys Leu Val Arg
1475 1480 1485
Arg Leu His His Lys Leu Lys Asn Gly Glu Cys Asn Glu Glu Phe
1490 1495 1500
Phe Leu Asp Leu Phe Asn Arg Glu Lys Lys Glu Ala Ile Leu Gln
1505 1510 1515
Leu Gly Glu Ile Leu Gly Leu Glu Asp Asp Leu Asn Glu Leu Ala
1520 1525 1530
Ser Ile Asn Trp Leu Asn Leu Asn Glu Met Phe Pro Leu Arg Met
1535 1540 1545
Val Leu Arg Gln Lys Val Val Tyr Pro Ser Val Met Thr Phe Gln
1550 1555 1560
Glu Glu Lys Ile Pro Ser Leu Ile Lys Thr Leu Gln Asn Lys Leu
1565 1570 1575
Cys Ser Lys Phe Thr Arg Gly Ala Gln Lys Leu Leu Ser Glu Ala
1580 1585 1590
Ile Asn Lys Ser Ala Phe Gln Ser Cys Val Ser Ser Gly Phe Ile
1595 1600 1605
Gly Leu Cys Lys Thr Leu Gly Ser Arg Cys Val Arg Asn Lys Asn
1610 1615 1620
Arg Glu Asn Met Tyr Ile Arg Lys Val Leu Glu Asp Leu Thr Met
1625 1630 1635
Asp Glu His Val Thr Arg Val His Lys Gln Asp Gly Val Met Leu
1640 1645 1650
Tyr Ile Cys Asp Lys Gln Arg His Pro Glu Ala His Arg Asp His
1655 1660 1665
Ile Asn Leu Leu Arg Pro Leu Leu Trp Asp Tyr Ile Cys Ile Ser
1670 1675 1680
Leu Ser Asn Ser Phe Glu Leu Gly Val Trp Val Leu Ala Glu Pro
1685 1690 1695
Val Lys Gly Lys Asn Glu Ser Asn Ser Ala Val Arg His Leu Asn
1700 1705 1710
Pro Cys Asp Tyr Val Ala Arg Lys Pro Glu Ser Ser Arg Leu Leu
1715 1720 1725
Glu Asp Lys Val Ser Leu Asn His Val Ile Gln Ser Val Arg Arg
1730 1735 1740
Leu Tyr Pro Lys Ile Phe Glu Asp Gln Leu Leu Pro Phe Met Ser
1745 1750 1755
Asp Val Ser Ser Lys Asn Met Arg Trp Ser Pro Arg Ile Lys Phe
1760 1765 1770
Leu Asp Leu Cys Val Leu Ile Asp Ile Asn Ser Glu Ser Leu Ser
1775 1780 1785
Leu Ile Ser His Val Val Lys Trp Lys Arg Asp Glu His Tyr Thr
1790 1795 1800
Val Leu Phe Ser Asp Leu Val Asn Ser His Gln Arg Ser Asp Ser
1805 1810 1815
Ser Leu Val Asp Glu Phe Val Val Ser Thr Arg Asp Val Cys Lys
1820 1825 1830
Asn Phe Leu Lys Gln Val Tyr Phe Glu Ser Phe Val Arg Glu Phe
1835 1840 1845
Val Ala Thr Ala Arg Thr Leu Gly Asn Phe Ser Trp Phe Pro His
1850 1855 1860
Lys Asp Met Met Pro Ser Glu Asp Gly Ala Glu Ala Leu Gly Pro
1865 1870 1875
Phe Gln Ser Phe Ile Leu Lys Val Val Asn Lys Lys Ile Glu Arg
1880 1885 1890
Pro Met Phe Arg Asn Asp Leu Gln Phe Gly Phe Gly Trp Phe Ser
1895 1900 1905
Tyr Arg Val Gly Asp Val Val Cys Asn Ala Ala Met Leu Ile Lys
1910 1915 1920
Gln Gly Leu Thr Asp Pro Lys Ala Phe Lys Ser Leu Arg Asp Leu
1925 1930 1935
Trp Asp Tyr Met Leu Ser Ser Thr Glu Gly Ile Leu Glu Phe Ser
1940 1945 1950
Ile Thr Val Asp Phe Thr His Asn Gln Asn Asn Thr Asp Cys Leu
1955 1960 1965
Arg Lys Phe Ser Leu Ile Phe Val Val Lys Cys Gln Leu Gln Ser
1970 1975 1980
Pro Gly Val Ala Asp Tyr Leu Ser Cys Ser His Ser Phe Lys Gly
1985 1990 1995
Glu Val Asp Arg Arg Leu Leu Asp Glu Cys Leu Asn Leu Leu Arg
2000 2005 2010
Thr Asp Pro Ile Phe Lys Ala Asn Asp Gly Val Phe Asp Ile Arg
2015 2020 2025
Ser Glu Glu Phe Glu Asp Tyr Met Glu Asp Pro Leu Thr Leu Gly
2030 2035 2040
Asp Ser Leu Glu Leu Glu Leu Ile Gly Ser Arg Arg Ile Leu Asn
2045 2050 2055
Glu Ile Lys Ser Thr Asp Phe Glu Arg Ile Gly Pro Glu Trp Glu
2060 2065 2070
Pro Val Pro Leu Thr Ile Arg Lys Gly Ala Leu Phe Glu Gly Arg
2075 2080 2085
Asn Phe Val Gln Asn Xaa Ser Val Lys Leu Glu Thr Lys Asp Met
2090 2095 2100
Arg Val Phe Leu Ala Glu Leu Glu Gly Cys Gly Lys Ile Gly Asp
2105 2110 2115
Val Leu Gly Ser Leu Leu Leu His Arg Phe Arg Thr Gly Glu His
2120 2125 2130
Leu Met Glu Ser Glu Ile Ser Xaa Val Leu Gln Glu Leu Cys Met
2135 2140 2145
Asp Arg Ser Val Met Leu Thr Pro Leu Ser Phe Val Pro Asp Trp
2150 2155 2160
Phe Thr Phe Arg Asp Cys Arg Leu Cys Phe Ser Arg Ser Lys Asn
2165 2170 2175
Thr Val Met Tyr Glu Thr Thr Gly Gly Arg Phe Arg Leu Lys Gly
2180 2185 2190
Lys Ser Cys Asp Asp Trp Leu Ala Glu Arg Val Ala Glu Glu Ile
2195 2200 2205
Asp
<210> 33
<211> 1497
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P91)
<400> 33
atgggtcaga ttgtgacaat gtttgaggct ttgcctcaca tcattgatga ggtcatcaac 60
attgtcatta ttgtgctcat tataatcacg agcatcaaag ctgtgtacaa tttcgccacc 120
tgtgggatat tagcactggt cagcttcctt tttttggctg gtaggtcctg tggcatgtac 180
ggccttaatg gtcccgacat ctataaaggg gtttaccagt tcaaatcagt ggagtttgat 240
atgtctcact taaatctgac gatgcccaat gcgtgctcag ccaacaactc tcatcactac 300
atcagtatgg gaagctctgg actggagcta actttcacta acgactccat ccttaatcac 360
aatttttgca acttaacctc cgctttcaac aaaaagactt ttgaccatac actcatgagt 420
atagtctcga gtctgcacct cagtattaga gggaattcca accacaaagc agtgtcttgt 480
gattttaaca atggcatcac cattcaatac aacttgtcat tttcggaccc acagagcgct 540
atgagccagt gttggacttt cagaggtaga gtcttggaca tgtttagaac tgcctttgga 600
ggaaaataca tgagaagtgg ctggggctgg gcaggttcag atggcaagac cacttggtgc 660
agccaaacaa gctatcagta cctaatcata caaaacagga cttgggaaaa ccactgtaga 720
tatgcaggcc cttttgggat gtctagaatc ctctttgctc aggaaaagac aaagtttctc 780
actaggagac ttgcaggcac attcacctgg accctgtcag actcctcagg agtagaaaat 840
ccaggtggtt attgcctgac caaatggatg atccttgctg cagagctcaa atgttttggg 900
aatacagctg ttgcaaaatg taatgtcaat catgatgaag agttctgtga catgctacga 960
ctaattgatt acaacaaggc cgccctgagt aagttcaagc aagatgtaga gtctgccttg 1020
catgtattca aaacaacagt aaattctctg atttccgatc agctgttgat gaggaatcat 1080
ctaagagatc taatgggggt accatactgt aattactcaa agttctggta tctggaacat 1140
gctaagactg gtgagactag tgtacccaag tgctggcttg tcactaatgg ctcctacttg 1200
aatgagaccc actttagtga tcaaatcgaa caagaagcag ataacatgat cacagagatg 1260
ttgaggaagg actacataaa aagacaaggg agtactcctt tagccttaat ggatcttttg 1320
atgttttcaa catcagcata tctaatcagc atctttctgc atcttgtgaa gataccaaca 1380
catagacaca taaagggcgg ttcatgtcca aagccacacc gcttgaccaa caaggggatc 1440
tgtagttgtg gtgcattcaa ggtgcctggt gtaaaaacta tctggaaaag acgctga 1497
<210> 34
<211> 498
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P91)
<400> 34
Met Gly Gln Ile Val Thr Met Phe Glu Ala Leu Pro His Ile Ile Asp
1 5 10 15
Glu Val Ile Asn Ile Val Ile Ile Val Leu Ile Ile Ile Thr Ser Ile
20 25 30
Lys Ala Val Tyr Asn Phe Ala Thr Cys Gly Ile Leu Ala Leu Val Ser
35 40 45
Phe Leu Phe Leu Ala Gly Arg Ser Cys Gly Met Tyr Gly Leu Asn Gly
50 55 60
Pro Asp Ile Tyr Lys Gly Val Tyr Gln Phe Lys Ser Val Glu Phe Asp
65 70 75 80
Met Ser His Leu Asn Leu Thr Met Pro Asn Ala Cys Ser Ala Asn Asn
85 90 95
Ser His His Tyr Ile Ser Met Gly Ser Ser Gly Leu Glu Leu Thr Phe
100 105 110
Thr Asn Asp Ser Ile Leu Asn His Asn Phe Cys Asn Leu Thr Ser Ala
115 120 125
Phe Asn Lys Lys Thr Phe Asp His Thr Leu Met Ser Ile Val Ser Ser
130 135 140
Leu His Leu Ser Ile Arg Gly Asn Ser Asn His Lys Ala Val Ser Cys
145 150 155 160
Asp Phe Asn Asn Gly Ile Thr Ile Gln Tyr Asn Leu Ser Phe Ser Asp
165 170 175
Pro Gln Ser Ala Met Ser Gln Cys Trp Thr Phe Arg Gly Arg Val Leu
180 185 190
Asp Met Phe Arg Thr Ala Phe Gly Gly Lys Tyr Met Arg Ser Gly Trp
195 200 205
Gly Trp Ala Gly Ser Asp Gly Lys Thr Thr Trp Cys Ser Gln Thr Ser
210 215 220
Tyr Gln Tyr Leu Ile Ile Gln Asn Arg Thr Trp Glu Asn His Cys Arg
225 230 235 240
Tyr Ala Gly Pro Phe Gly Met Ser Arg Ile Leu Phe Ala Gln Glu Lys
245 250 255
Thr Lys Phe Leu Thr Arg Arg Leu Ala Gly Thr Phe Thr Trp Thr Leu
260 265 270
Ser Asp Ser Ser Gly Val Glu Asn Pro Gly Gly Tyr Cys Leu Thr Lys
275 280 285
Trp Met Ile Leu Ala Ala Glu Leu Lys Cys Phe Gly Asn Thr Ala Val
290 295 300
Ala Lys Cys Asn Val Asn His Asp Glu Glu Phe Cys Asp Met Leu Arg
305 310 315 320
Leu Ile Asp Tyr Asn Lys Ala Ala Leu Ser Lys Phe Lys Gln Asp Val
325 330 335
Glu Ser Ala Leu His Val Phe Lys Thr Thr Val Asn Ser Leu Ile Ser
340 345 350
Asp Gln Leu Leu Met Arg Asn His Leu Arg Asp Leu Met Gly Val Pro
355 360 365
Tyr Cys Asn Tyr Ser Lys Phe Trp Tyr Leu Glu His Ala Lys Thr Gly
370 375 380
Glu Thr Ser Val Pro Lys Cys Trp Leu Val Thr Asn Gly Ser Tyr Leu
385 390 395 400
Asn Glu Thr His Phe Ser Asp Gln Ile Glu Gln Glu Ala Asp Asn Met
405 410 415
Ile Thr Glu Met Leu Arg Lys Asp Tyr Ile Lys Arg Gln Gly Ser Thr
420 425 430
Pro Leu Ala Leu Met Asp Leu Leu Met Phe Ser Thr Ser Ala Tyr Leu
435 440 445
Ile Ser Ile Phe Leu His Leu Val Lys Ile Pro Thr His Arg His Ile
450 455 460
Lys Gly Gly Ser Cys Pro Lys Pro His Arg Leu Thr Asn Lys Gly Ile
465 470 475 480
Cys Ser Cys Gly Ala Phe Lys Val Pro Gly Val Lys Thr Ile Trp Lys
485 490 495
Arg Arg
<210> 35
<211> 1677
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P91)
<400> 35
atgtctttgt ccaaagaagt caaaagcttt cagtggacac aggcgttgag gagggagttg 60
cagagtttta catcagatgt aaaggctgcc gtcatcaagg acgcaaccag tcttctaaat 120
gggttggact tttctgaagt cagcaacgtt cagaggatca tgagaaagga aaggagggat 180
gataaagact tgcagagact caggagtctt aaccagactg tgcattctct tgttgatctg 240
aagtctacat caaagaaaaa tgttctgaaa gtgggaagac ttagtgcaga ggaattgatg 300
acccttgcag ctgatcttga gaagctgaag gccaaaatta tgagaactga gaggcctcaa 360
gcttctggag tctacatggg aaatttgaca gcacaacaac ttgatcaaag atcccaaata 420
ctgcaaatgg ttgggatgag aagacctcag cagggtgcaa gtggtgtagt aagggtttgg 480
gatgtgaagg actcatcact tctgaacaat cagttcggca caatgccaag cctgacaatg 540
gcttgcatgg caaaacagtc acagacccca ctcaatgatg ttgtgcaggc actcacagac 600
cttggcttac tttacacagt caaatacccg aatctcagtg atcttgaaag gctaaaggat 660
aaacacccag ttctgggggt cattactgaa cagcaatcta gtatcaatat ctctggttat 720
aatttcagtc ttggtgcagc tgtgaaagcg ggggcagctc tgctagatgg agggaacatg 780
ctggaatcta tcttgatcaa accgagcaac agtgaggatc tcctaaaagc agtcctcggg 840
gccaagaaga aactcaacat gtttgtctca gatcaagttg gagatagaaa tccctatgaa 900
aacatccttt ataaagtctg tctttcaggt gaaggatggc catacatagc ctgtagaacg 960
tcagttgtgg ggagagcatg ggagaacaca acaattgatc tcacaaatga aaaacttgtt 1020
gccaactcat ctaggccagt gcctggagca gcaggcccac ctcaggtggg cttgagttac 1080
agtcagacaa tgctgttgaa agacttgatg ggagggattg atcccaatgc tcccacatgg 1140
attgacattg agggcaggtt caatgatcca gtggagatag caatattcca accacaaaat 1200
gggcaattca tacattttta cagggaacct acggaccaga agcaattcaa gcaggactca 1260
aagtattcac acggcatgga tcttgctgat ctcttcaatg cacagcctgg gctgacctca 1320
tcagttatag gtgctctccc acaagggatg gttttgagct gtcaaggttc tgatgacatc 1380
agaaagcttc tggactcaca aaatagaagg gacataaaac tcattgatgt tgagatgacc 1440
aaggaggcct caagagaata tgaagataaa gtgtgggaca aatatggctg gctatgcaaa 1500
atgcacactg gggtagtgag agacaaaaag aagaaagaga tcaccccaca ctgtgcactc 1560
atggactgca tcatttttga gagtgcttcc aaggcaagac tccctgatct aaaaaccgtt 1620
cacaacatcc tgccacatga tttaatcttc agaggaccca atgttgtgac actctaa 1677
<210> 36
<211> 558
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P91)
<400> 36
Met Ser Leu Ser Lys Glu Val Lys Ser Phe Gln Trp Thr Gln Ala Leu
1 5 10 15
Arg Arg Glu Leu Gln Ser Phe Thr Ser Asp Val Lys Ala Ala Val Ile
20 25 30
Lys Asp Ala Thr Ser Leu Leu Asn Gly Leu Asp Phe Ser Glu Val Ser
35 40 45
Asn Val Gln Arg Ile Met Arg Lys Glu Arg Arg Asp Asp Lys Asp Leu
50 55 60
Gln Arg Leu Arg Ser Leu Asn Gln Thr Val His Ser Leu Val Asp Leu
65 70 75 80
Lys Ser Thr Ser Lys Lys Asn Val Leu Lys Val Gly Arg Leu Ser Ala
85 90 95
Glu Glu Leu Met Thr Leu Ala Ala Asp Leu Glu Lys Leu Lys Ala Lys
100 105 110
Ile Met Arg Thr Glu Arg Pro Gln Ala Ser Gly Val Tyr Met Gly Asn
115 120 125
Leu Thr Ala Gln Gln Leu Asp Gln Arg Ser Gln Ile Leu Gln Met Val
130 135 140
Gly Met Arg Arg Pro Gln Gln Gly Ala Ser Gly Val Val Arg Val Trp
145 150 155 160
Asp Val Lys Asp Ser Ser Leu Leu Asn Asn Gln Phe Gly Thr Met Pro
165 170 175
Ser Leu Thr Met Ala Cys Met Ala Lys Gln Ser Gln Thr Pro Leu Asn
180 185 190
Asp Val Val Gln Ala Leu Thr Asp Leu Gly Leu Leu Tyr Thr Val Lys
195 200 205
Tyr Pro Asn Leu Ser Asp Leu Glu Arg Leu Lys Asp Lys His Pro Val
210 215 220
Leu Gly Val Ile Thr Glu Gln Gln Ser Ser Ile Asn Ile Ser Gly Tyr
225 230 235 240
Asn Phe Ser Leu Gly Ala Ala Val Lys Ala Gly Ala Ala Leu Leu Asp
245 250 255
Gly Gly Asn Met Leu Glu Ser Ile Leu Ile Lys Pro Ser Asn Ser Glu
260 265 270
Asp Leu Leu Lys Ala Val Leu Gly Ala Lys Lys Lys Leu Asn Met Phe
275 280 285
Val Ser Asp Gln Val Gly Asp Arg Asn Pro Tyr Glu Asn Ile Leu Tyr
290 295 300
Lys Val Cys Leu Ser Gly Glu Gly Trp Pro Tyr Ile Ala Cys Arg Thr
305 310 315 320
Ser Val Val Gly Arg Ala Trp Glu Asn Thr Thr Ile Asp Leu Thr Asn
325 330 335
Glu Lys Leu Val Ala Asn Ser Ser Arg Pro Val Pro Gly Ala Ala Gly
340 345 350
Pro Pro Gln Val Gly Leu Ser Tyr Ser Gln Thr Met Leu Leu Lys Asp
355 360 365
Leu Met Gly Gly Ile Asp Pro Asn Ala Pro Thr Trp Ile Asp Ile Glu
370 375 380
Gly Arg Phe Asn Asp Pro Val Glu Ile Ala Ile Phe Gln Pro Gln Asn
385 390 395 400
Gly Gln Phe Ile His Phe Tyr Arg Glu Pro Thr Asp Gln Lys Gln Phe
405 410 415
Lys Gln Asp Ser Lys Tyr Ser His Gly Met Asp Leu Ala Asp Leu Phe
420 425 430
Asn Ala Gln Pro Gly Leu Thr Ser Ser Val Ile Gly Ala Leu Pro Gln
435 440 445
Gly Met Val Leu Ser Cys Gln Gly Ser Asp Asp Ile Arg Lys Leu Leu
450 455 460
Asp Ser Gln Asn Arg Arg Asp Ile Lys Leu Ile Asp Val Glu Met Thr
465 470 475 480
Lys Glu Ala Ser Arg Glu Tyr Glu Asp Lys Val Trp Asp Lys Tyr Gly
485 490 495
Trp Leu Cys Lys Met His Thr Gly Val Val Arg Asp Lys Lys Lys Lys
500 505 510
Glu Ile Thr Pro His Cys Ala Leu Met Asp Cys Ile Ile Phe Glu Ser
515 520 525
Ala Ser Lys Ala Arg Leu Pro Asp Leu Lys Thr Val His Asn Ile Leu
530 535 540
Pro His Asp Leu Ile Phe Arg Gly Pro Asn Val Val Thr Leu
545 550 555
<210> 37
<211> 273
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P91)
<400> 37
atgggccaag gcaagtccaa agaagaaagg gacaccagca atacaggcag agcagagctt 60
ttgccagaca ccacctatct tggtcctcta aattgtaaat catgttggca gaaatttgac 120
agcttggtta gatgccatga ccactatctt tgcagacact gtctgaatct cctgctgtca 180
gtttccgaca gatgtcctct ctgtaagtat ccactgccaa ccaaactgaa ggtgtcaaca 240
gtcccaagct ccccacctcc ctatgaggag tga 273
<210> 38
<211> 90
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P91)
<400> 38
Met Gly Gln Gly Lys Ser Lys Glu Glu Arg Asp Thr Ser Asn Thr Gly
1 5 10 15
Arg Ala Glu Leu Leu Pro Asp Thr Thr Tyr Leu Gly Pro Leu Asn Cys
20 25 30
Lys Ser Cys Trp Gln Lys Phe Asp Ser Leu Val Arg Cys His Asp His
35 40 45
Tyr Leu Cys Arg His Cys Leu Asn Leu Leu Leu Ser Val Ser Asp Arg
50 55 60
Cys Pro Leu Cys Lys Tyr Pro Leu Pro Thr Lys Leu Lys Val Ser Thr
65 70 75 80
Val Pro Ser Ser Pro Pro Pro Tyr Glu Glu
85 90
<210> 39
<211> 6630
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P91)
<400> 39
atggatgaaa ctattgcaga tttgagagag ttgtgtctaa attacataga acaggacgag 60
aggctgtcaa ggcaaaaact caacttcctg ggacaaagag aacccagaat ggtgctaatt 120
gagggactca aattgttatc acgctgtata gagatagaca gtgcagacaa aagtggttgc 180
atacacaacc acgatgacaa atctgttgaa acaatcctaa tagactctgg gattgtgtgt 240
ccaggactgc cactcatcat ccctgatggt tataagttga ttgacaattc ccttattctt 300
cttgaatgtt ttgttagaag cacaccagct agttttgaaa agaagttcat tgaggacacc 360
aacaaactag catgcatcaa agaagatctt gctgttgcag gcatcacact ggttccaata 420
gtggatggtc gttgtgatta tgataacagt ttcatgccag aatgggtgaa ttttaagttc 480
agagacctcc tatttaaact cctggagtat tctagtcaag atgagaaagt ttttgaggag 540
tctgaatact tcaggctctg tgagtctctt aagaccactg ttgacaaacg ttccggcatg 600
gactcaatga aaattttgaa agacgcaaga tcatttcata acgatgagat tatgaaaatg 660
tgccacgatg gtgtcaaccc caacatgagt tgcgatgatg tggtctttgg cataaattcc 720
ttttttggca ggtttaggag ggacctgtta aatgggaaac tcaaaaggaa tttccaaaag 780
gtcagccctg ggggcttaat caaggaattc tctgaacttt atgaaaccct tactgataat 840
gatgacatat taatgttgag caaagaggca gttgaatcct gccccttaat gaggttcatt 900
acagcagaga cccatgggca tgagagagga agcgatgcta acactgagta tgaaaggcta 960
ctctctatgt tgaacaaggt gaaaagttta aaattattaa acactagaag gagacagctg 1020
ctgaacttag atgtcttatg tctttcttca cttattaagc agtcaatttc caaagggttg 1080
gaaaatgata aacattgggt tggttgctgc tacagtagtg tgaatgatag gcttgtgagc 1140
cttcaaagta ccaaagaaga attcatgaga cttttgaaga acagaagaaa atcaagagtg 1200
cacaaaaagg catctcttga tgagcttttt agggtatcca taaatgagtt catagcaaaa 1260
atccagaaat gcctatcaac agtgggactt agttttgagc attacggact atcagaatgc 1320
ctcgtgcaag aatgccatat accatttgct gaatttgaga actttatgag agccgggact 1380
catcctgtaa tgcattacac aaaatttgaa gattacactt tccagcctaa catagagcaa 1440
ttgaggggtt tacagagttt gagaaaactg tcatctgttt gtttggctct aacaaacagc 1500
atgaaaacaa gctcagttgc aaggttgaga cagaaccaac tggggtctgt gagatatcaa 1560
gtggtggagt gcaaagaggt gttttgccag ataataaaac tggattccga agagtatcat 1620
ctactatatc agaaaactgg agaatcatcg aggtgttatt ccatacaagg tccggatggt 1680
cacttgattt ccttttacgc agatccaaaa aggttctttt taccaatttt ttcagatgag 1740
gtgttgcaca acatgataga cacaatgatt tcatggatta ggtcatgccc tgacttaaaa 1800
gattctctta ttgacattga gactgcacta aggacattga tcctactgat gctcaccaac 1860
ccaacaaaga gaaatcaaaa gcaggttcaa aatattaggt atttagtgat ggccatcgtc 1920
tcagactttt catcgacctc attaatggat aagttgaagg aggatctaat cacacctgcc 1980
gagaaagtgg tgtacaggct gcttcggttt ttgattagga caatttttgg tactggtgaa 2040
aaggtgttat tgagtgcaaa attcaagttt atgttgaatg tgtcatacct gtgtcatttg 2100
atcacaaagg agacccctga tagattgaca gatcagataa aatgttttga aaagttcttt 2160
gagcccaaga gtgagtttgg tttctttgtc aaccctaagg aaacaatcac acccgaagag 2220
gaatgtgttt tttatgaaca aatgaagaag ttcaccggta aagatattga ttgtcagcat 2280
tcaacccctg gtgttaattt agagatcttt agcatgatgg tatcttcatt caacaatggc 2340
accttaattc taaaagggga gaaaaggctc aacaatctgg accccatgac caactctgga 2400
tgtgcgacag cattagatct cgcaagcaac aaaagtgtgg ttgtcaataa acatctgaat 2460
ggagaacggc ttttggagta tgattttaac aaattgcttg ttagtgctgt gagccaaatt 2520
acagagggct tcatgaggaa acaaaagtat aagctgagac actcagatta cgaatataag 2580
gtctcaaagc ttgtctctag attagtcatc ggttccagga aaacagaagt agacaaattg 2640
gaagatgatc cggtagatgt gtgtttcgag ggggaggagg agacaagttt tttcaggagt 2700
ttagaagata aggtcagctc cacaataaca cggtataata gaggcactag gcttaatgaa 2760
gggcaagggg agggagaatt caagaacaca aaaggactac accaccttca gattattttg 2820
tcaggtaaaa gagcttatct gaggaaagtc attttatcag aaatttcatt tcatctagta 2880
gaggactttg atccatcctg tctcaccaat gacgacatga ggtttatttg tgaggctgtt 2940
gaaggttcaa cagaactgtc accattgtat tttacatcag ctgtcaaaga acaatgtggt 3000
ctggatgaga tggcaagaaa cctctgtaga aagttcttct cagagggtga ttggttctca 3060
tgtatgaaga tgatcttgtt acagatgaat gcaaatgcgt attcagggaa gtacagacac 3120
atgcagaggc agagcttaaa ttttaaattt gactgggaca aattggaaga agatgtaaga 3180
attagtgaaa gggaaagcaa ttctgaatct ctaagtaagg ccctttcatt gacaaaatgc 3240
atgagtgctg ctctaaagaa tctgtgtttt tactcagaag aatcaccaac atcatacact 3300
tcagttggcc ctgactctgg gagactaaaa tttgcattgt catacaaaga gcaggttggg 3360
ggaaatagag agctttacat tggggatttg aggacaaaaa tgttcacaag attggtagaa 3420
gattattttg aatccttttc tagtttcttt tcaggatctt gtttaaacaa tgataaagag 3480
tttgaaaatg caatcttgtc aatgactatc aatgtgagag aagggttgtt aaactacagc 3540
atggatcaca gcaaatgggg accaatgatg tgcccattcc tattcttaat gcttctccaa 3600
aatctcaaac tgggtgatga tcagtacgtg cgttctggaa aagatcatgt tagcaccttg 3660
ttgacttggc atatgcataa acttgttgaa gtccctttcc ctgttgtgaa tgcaatgatg 3720
aaatcatatg ttaaatcaaa actcaagctt ctcaaagggt caggaacgac tgttacggag 3780
agaatcttta gagagtattt tgaaatgggg gtggtgccat ctcacatatc tagtctcatt 3840
gacatgggac aggggatcct acacaatgct tctgattttt acggtttaat tagtgaaagg 3900
tttatcaatt attgtattgg tgtcattttt ggagagaggc cagaagccta tacatcaagt 3960
gatgatcaga tcactttatt tgacaagaga ttgagtgact tagttgatag tgacccagaa 4020
gaagtccttg tcttgctgga attccactct cacttaagtg gtttgttgaa caagttcatc 4080
agtccaaaaa gtgtggttgg gcggtttgca gcggaattca aatccagatt ttatgtgtgg 4140
ggggaggagg tccctctcct cacgaaattt gtgtctgcgg cactacacaa tgttaagtgt 4200
aaagaaccgc atcaactttg tgagacaata gatacgattg ctgatcaagc tatagcaaat 4260
ggagttccag tttttttagt aaactgtatc cagaggagga cactggatct cttgaaatat 4320
gctaatttcc ctttagatcc attcttgtta aacactcaca ctgatgtaaa ggattggtta 4380
gatggttcta gaggttatag aatccaaaga ctcattgaag aattgtgtcc cagtgaaaca 4440
aagatcatga gaaaacttgt aagaagacta catcacaaac tcaagaacgg tgaatgtaac 4500
gaggaatttt ttctagacct cttcaacagg gaaaaggaag aggccatcct tcaattggga 4560
gagattcttg gtcttgagga tgatcttaat gagttggcaa gcatcaattg gttgaatctg 4620
aatgaaatgt tcccattgag gatggttctg agacaaaaag tggtttaccc atcagtaatg 4680
acctttcaag aggaaaagat cccctcattg attaaaacac tccaaaataa gctttgtagt 4740
aagttcacaa gaggtgcaca gaagctgttg tcagaggcaa tcaacaaatc agcttttcag 4800
agttgtgtct catccggctt tataggtctc tgtaagactt taggaagtag gtgtgtgaga 4860
aataaaaaca gggaaaatat gtatatcaga aaggtgcttg aagatctgac catggatgaa 4920
catgtcacaa gggttcacaa acaagatggt gtgatgttgt acatttgcga caagcagaga 4980
cacccagagg ctcaccgtga ccacatcaac cttttgaggc cccttctctg ggactacatt 5040
tgcatctcat tgagcaactc ttttgagctg ggtgtttggg ttttagcaga acctgtgaaa 5100
ggaaagaacg agagtaattc ggctgttagg cacttaaatc catgtgatta tgtagcaaga 5160
aaacctgaga gttcgagact actagaggat aaagtgagtt tgaatcatgt aattcaatct 5220
gtgaggcgac tgtaccccaa aatctttgag gatcagttgc tcccattcat gtctgatgtg 5280
agctcaaaaa atatgagatg gagtcccagg attaaattcc ttgacctttg tgtgctgatt 5340
gacatcaact cagagtcttt gtcactcatt tctcatgttg tcaaatggaa gagggacgaa 5400
cattacactg tgctgttttc tgatctcgtc aactctcacc aacggtcaga ctcaagttta 5460
gttgatgaat ttgttgtcag cacaagggat gtctgcaaga actttttgaa gcaagtgtat 5520
ttcgaatcat ttgtacgaga gtttgttgca acagctagga ccttaggtaa cttttcatgg 5580
ttcccccata aggacatgat gccatctgaa gatggcgctg aagcactggg acccttccaa 5640
tcatttattt tgaaagtggt gaacaagaaa atagagaggc ccatgtttag gaatgacttg 5700
cagtttggtt ttggttggtt ctcttatcgt gtgggggatg ttgtgtgtaa tgccgctatg 5760
ttaattaagc agggtttgac agatccaaaa gcatttaaat ctttaagaga tttgtgggat 5820
tacatgctca gcagcacaga ggggatattg gagttctcaa tcacagtgga tttcacacac 5880
aaccagaaca acactgactg cttgaggaaa ttttcattga tctttgtggt taaatgccaa 5940
ttacagagtc caggtgtagc tgattactta tcgtgctctc attccttcaa aggtgaggtt 6000
gacaggagat tattagatga gtgtctcaat ctgttgagga cagaccccat ctttaaagcg 6060
aatgatggag tctttgacat taggtctgaa gagtttgaag attacatgga agaccctttg 6120
acacttggtg attcactaga acttgaacta ataggttcta gaaggattct gaatgagatc 6180
aaatctactg actttgagag gatagggcct gagtgggaac ctgtgcctct gaccataagg 6240
aagggtgccc tctttgaggg gaggaacttt gttcagaata tctctgtgaa attggagaca 6300
aaggacatga gggtctttct ggcagagctc gagggctgtg gaaaaattgg tgatgtcctc 6360
ggcagcctcc tcctgcaccg attcagaact ggtgagcact tgatggagtc agaaataagt 6420
acagttcttc aggagctctg catggacaga tccgtcatgc tgacaccatt atcttttgtg 6480
ccagattggt tcaccttcag agattgtagg ctctgcttca gcargtcaaa gaacactgta 6540
atgtatgaga caactggggg caggttcaga ctcaagggga aatcctgtga cgattggctg 6600
gcggagcggg tggccgagga gatcgactag 6630
<210> 40
<211> 2209
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P91)
<220>
<221> MISC_FEATURE
<222> (2175)..(2175)
<223> Xaa可以是Arg或Lys
<400> 40
Met Asp Glu Thr Ile Ala Asp Leu Arg Glu Leu Cys Leu Asn Tyr Ile
1 5 10 15
Glu Gln Asp Glu Arg Leu Ser Arg Gln Lys Leu Asn Phe Leu Gly Gln
20 25 30
Arg Glu Pro Arg Met Val Leu Ile Glu Gly Leu Lys Leu Leu Ser Arg
35 40 45
Cys Ile Glu Ile Asp Ser Ala Asp Lys Ser Gly Cys Ile His Asn His
50 55 60
Asp Asp Lys Ser Val Glu Thr Ile Leu Ile Asp Ser Gly Ile Val Cys
65 70 75 80
Pro Gly Leu Pro Leu Ile Ile Pro Asp Gly Tyr Lys Leu Ile Asp Asn
85 90 95
Ser Leu Ile Leu Leu Glu Cys Phe Val Arg Ser Thr Pro Ala Ser Phe
100 105 110
Glu Lys Lys Phe Ile Glu Asp Thr Asn Lys Leu Ala Cys Ile Lys Glu
115 120 125
Asp Leu Ala Val Ala Gly Ile Thr Leu Val Pro Ile Val Asp Gly Arg
130 135 140
Cys Asp Tyr Asp Asn Ser Phe Met Pro Glu Trp Val Asn Phe Lys Phe
145 150 155 160
Arg Asp Leu Leu Phe Lys Leu Leu Glu Tyr Ser Ser Gln Asp Glu Lys
165 170 175
Val Phe Glu Glu Ser Glu Tyr Phe Arg Leu Cys Glu Ser Leu Lys Thr
180 185 190
Thr Val Asp Lys Arg Ser Gly Met Asp Ser Met Lys Ile Leu Lys Asp
195 200 205
Ala Arg Ser Phe His Asn Asp Glu Ile Met Lys Met Cys His Asp Gly
210 215 220
Val Asn Pro Asn Met Ser Cys Asp Asp Val Val Phe Gly Ile Asn Ser
225 230 235 240
Phe Phe Gly Arg Phe Arg Arg Asp Leu Leu Asn Gly Lys Leu Lys Arg
245 250 255
Asn Phe Gln Lys Val Ser Pro Gly Gly Leu Ile Lys Glu Phe Ser Glu
260 265 270
Leu Tyr Glu Thr Leu Thr Asp Asn Asp Asp Ile Leu Met Leu Ser Lys
275 280 285
Glu Ala Val Glu Ser Cys Pro Leu Met Arg Phe Ile Thr Ala Glu Thr
290 295 300
His Gly His Glu Arg Gly Ser Asp Ala Asn Thr Glu Tyr Glu Arg Leu
305 310 315 320
Leu Ser Met Leu Asn Lys Val Lys Ser Leu Lys Leu Leu Asn Thr Arg
325 330 335
Arg Arg Gln Leu Leu Asn Leu Asp Val Leu Cys Leu Ser Ser Leu Ile
340 345 350
Lys Gln Ser Ile Ser Lys Gly Leu Glu Asn Asp Lys His Trp Val Gly
355 360 365
Cys Cys Tyr Ser Ser Val Asn Asp Arg Leu Val Ser Leu Gln Ser Thr
370 375 380
Lys Glu Glu Phe Met Arg Leu Leu Lys Asn Arg Arg Lys Ser Arg Val
385 390 395 400
His Lys Lys Ala Ser Leu Asp Glu Leu Phe Arg Val Ser Ile Asn Glu
405 410 415
Phe Ile Ala Lys Ile Gln Lys Cys Leu Ser Thr Val Gly Leu Ser Phe
420 425 430
Glu His Tyr Gly Leu Ser Glu Cys Leu Val Gln Glu Cys His Ile Pro
435 440 445
Phe Ala Glu Phe Glu Asn Phe Met Arg Ala Gly Thr His Pro Val Met
450 455 460
His Tyr Thr Lys Phe Glu Asp Tyr Thr Phe Gln Pro Asn Ile Glu Gln
465 470 475 480
Leu Arg Gly Leu Gln Ser Leu Arg Lys Leu Ser Ser Val Cys Leu Ala
485 490 495
Leu Thr Asn Ser Met Lys Thr Ser Ser Val Ala Arg Leu Arg Gln Asn
500 505 510
Gln Leu Gly Ser Val Arg Tyr Gln Val Val Glu Cys Lys Glu Val Phe
515 520 525
Cys Gln Ile Ile Lys Leu Asp Ser Glu Glu Tyr His Leu Leu Tyr Gln
530 535 540
Lys Thr Gly Glu Ser Ser Arg Cys Tyr Ser Ile Gln Gly Pro Asp Gly
545 550 555 560
His Leu Ile Ser Phe Tyr Ala Asp Pro Lys Arg Phe Phe Leu Pro Ile
565 570 575
Phe Ser Asp Glu Val Leu His Asn Met Ile Asp Thr Met Ile Ser Trp
580 585 590
Ile Arg Ser Cys Pro Asp Leu Lys Asp Ser Leu Ile Asp Ile Glu Thr
595 600 605
Ala Leu Arg Thr Leu Ile Leu Leu Met Leu Thr Asn Pro Thr Lys Arg
610 615 620
Asn Gln Lys Gln Val Gln Asn Ile Arg Tyr Leu Val Met Ala Ile Val
625 630 635 640
Ser Asp Phe Ser Ser Thr Ser Leu Met Asp Lys Leu Lys Glu Asp Leu
645 650 655
Ile Thr Pro Ala Glu Lys Val Val Tyr Arg Leu Leu Arg Phe Leu Ile
660 665 670
Arg Thr Ile Phe Gly Thr Gly Glu Lys Val Leu Leu Ser Ala Lys Phe
675 680 685
Lys Phe Met Leu Asn Val Ser Tyr Leu Cys His Leu Ile Thr Lys Glu
690 695 700
Thr Pro Asp Arg Leu Thr Asp Gln Ile Lys Cys Phe Glu Lys Phe Phe
705 710 715 720
Glu Pro Lys Ser Glu Phe Gly Phe Phe Val Asn Pro Lys Glu Thr Ile
725 730 735
Thr Pro Glu Glu Glu Cys Val Phe Tyr Glu Gln Met Lys Lys Phe Thr
740 745 750
Gly Lys Asp Ile Asp Cys Gln His Ser Thr Pro Gly Val Asn Leu Glu
755 760 765
Ile Phe Ser Met Met Val Ser Ser Phe Asn Asn Gly Thr Leu Ile Leu
770 775 780
Lys Gly Glu Lys Arg Leu Asn Asn Leu Asp Pro Met Thr Asn Ser Gly
785 790 795 800
Cys Ala Thr Ala Leu Asp Leu Ala Ser Asn Lys Ser Val Val Val Asn
805 810 815
Lys His Leu Asn Gly Glu Arg Leu Leu Glu Tyr Asp Phe Asn Lys Leu
820 825 830
Leu Val Ser Ala Val Ser Gln Ile Thr Glu Gly Phe Met Arg Lys Gln
835 840 845
Lys Tyr Lys Leu Arg His Ser Asp Tyr Glu Tyr Lys Val Ser Lys Leu
850 855 860
Val Ser Arg Leu Val Ile Gly Ser Arg Lys Thr Glu Val Asp Lys Leu
865 870 875 880
Glu Asp Asp Pro Val Asp Val Cys Phe Glu Gly Glu Glu Glu Thr Ser
885 890 895
Phe Phe Arg Ser Leu Glu Asp Lys Val Ser Ser Thr Ile Thr Arg Tyr
900 905 910
Asn Arg Gly Thr Arg Leu Asn Glu Gly Gln Gly Glu Gly Glu Phe Lys
915 920 925
Asn Thr Lys Gly Leu His His Leu Gln Ile Ile Leu Ser Gly Lys Arg
930 935 940
Ala Tyr Leu Arg Lys Val Ile Leu Ser Glu Ile Ser Phe His Leu Val
945 950 955 960
Glu Asp Phe Asp Pro Ser Cys Leu Thr Asn Asp Asp Met Arg Phe Ile
965 970 975
Cys Glu Ala Val Glu Gly Ser Thr Glu Leu Ser Pro Leu Tyr Phe Thr
980 985 990
Ser Ala Val Lys Glu Gln Cys Gly Leu Asp Glu Met Ala Arg Asn Leu
995 1000 1005
Cys Arg Lys Phe Phe Ser Glu Gly Asp Trp Phe Ser Cys Met Lys
1010 1015 1020
Met Ile Leu Leu Gln Met Asn Ala Asn Ala Tyr Ser Gly Lys Tyr
1025 1030 1035
Arg His Met Gln Arg Gln Ser Leu Asn Phe Lys Phe Asp Trp Asp
1040 1045 1050
Lys Leu Glu Glu Asp Val Arg Ile Ser Glu Arg Glu Ser Asn Ser
1055 1060 1065
Glu Ser Leu Ser Lys Ala Leu Ser Leu Thr Lys Cys Met Ser Ala
1070 1075 1080
Ala Leu Lys Asn Leu Cys Phe Tyr Ser Glu Glu Ser Pro Thr Ser
1085 1090 1095
Tyr Thr Ser Val Gly Pro Asp Ser Gly Arg Leu Lys Phe Ala Leu
1100 1105 1110
Ser Tyr Lys Glu Gln Val Gly Gly Asn Arg Glu Leu Tyr Ile Gly
1115 1120 1125
Asp Leu Arg Thr Lys Met Phe Thr Arg Leu Val Glu Asp Tyr Phe
1130 1135 1140
Glu Ser Phe Ser Ser Phe Phe Ser Gly Ser Cys Leu Asn Asn Asp
1145 1150 1155
Lys Glu Phe Glu Asn Ala Ile Leu Ser Met Thr Ile Asn Val Arg
1160 1165 1170
Glu Gly Leu Leu Asn Tyr Ser Met Asp His Ser Lys Trp Gly Pro
1175 1180 1185
Met Met Cys Pro Phe Leu Phe Leu Met Leu Leu Gln Asn Leu Lys
1190 1195 1200
Leu Gly Asp Asp Gln Tyr Val Arg Ser Gly Lys Asp His Val Ser
1205 1210 1215
Thr Leu Leu Thr Trp His Met His Lys Leu Val Glu Val Pro Phe
1220 1225 1230
Pro Val Val Asn Ala Met Met Lys Ser Tyr Val Lys Ser Lys Leu
1235 1240 1245
Lys Leu Leu Lys Gly Ser Gly Thr Thr Val Thr Glu Arg Ile Phe
1250 1255 1260
Arg Glu Tyr Phe Glu Met Gly Val Val Pro Ser His Ile Ser Ser
1265 1270 1275
Leu Ile Asp Met Gly Gln Gly Ile Leu His Asn Ala Ser Asp Phe
1280 1285 1290
Tyr Gly Leu Ile Ser Glu Arg Phe Ile Asn Tyr Cys Ile Gly Val
1295 1300 1305
Ile Phe Gly Glu Arg Pro Glu Ala Tyr Thr Ser Ser Asp Asp Gln
1310 1315 1320
Ile Thr Leu Phe Asp Lys Arg Leu Ser Asp Leu Val Asp Ser Asp
1325 1330 1335
Pro Glu Glu Val Leu Val Leu Leu Glu Phe His Ser His Leu Ser
1340 1345 1350
Gly Leu Leu Asn Lys Phe Ile Ser Pro Lys Ser Val Val Gly Arg
1355 1360 1365
Phe Ala Ala Glu Phe Lys Ser Arg Phe Tyr Val Trp Gly Glu Glu
1370 1375 1380
Val Pro Leu Leu Thr Lys Phe Val Ser Ala Ala Leu His Asn Val
1385 1390 1395
Lys Cys Lys Glu Pro His Gln Leu Cys Glu Thr Ile Asp Thr Ile
1400 1405 1410
Ala Asp Gln Ala Ile Ala Asn Gly Val Pro Val Phe Leu Val Asn
1415 1420 1425
Cys Ile Gln Arg Arg Thr Leu Asp Leu Leu Lys Tyr Ala Asn Phe
1430 1435 1440
Pro Leu Asp Pro Phe Leu Leu Asn Thr His Thr Asp Val Lys Asp
1445 1450 1455
Trp Leu Asp Gly Ser Arg Gly Tyr Arg Ile Gln Arg Leu Ile Glu
1460 1465 1470
Glu Leu Cys Pro Ser Glu Thr Lys Ile Met Arg Lys Leu Val Arg
1475 1480 1485
Arg Leu His His Lys Leu Lys Asn Gly Glu Cys Asn Glu Glu Phe
1490 1495 1500
Phe Leu Asp Leu Phe Asn Arg Glu Lys Glu Glu Ala Ile Leu Gln
1505 1510 1515
Leu Gly Glu Ile Leu Gly Leu Glu Asp Asp Leu Asn Glu Leu Ala
1520 1525 1530
Ser Ile Asn Trp Leu Asn Leu Asn Glu Met Phe Pro Leu Arg Met
1535 1540 1545
Val Leu Arg Gln Lys Val Val Tyr Pro Ser Val Met Thr Phe Gln
1550 1555 1560
Glu Glu Lys Ile Pro Ser Leu Ile Lys Thr Leu Gln Asn Lys Leu
1565 1570 1575
Cys Ser Lys Phe Thr Arg Gly Ala Gln Lys Leu Leu Ser Glu Ala
1580 1585 1590
Ile Asn Lys Ser Ala Phe Gln Ser Cys Val Ser Ser Gly Phe Ile
1595 1600 1605
Gly Leu Cys Lys Thr Leu Gly Ser Arg Cys Val Arg Asn Lys Asn
1610 1615 1620
Arg Glu Asn Met Tyr Ile Arg Lys Val Leu Glu Asp Leu Thr Met
1625 1630 1635
Asp Glu His Val Thr Arg Val His Lys Gln Asp Gly Val Met Leu
1640 1645 1650
Tyr Ile Cys Asp Lys Gln Arg His Pro Glu Ala His Arg Asp His
1655 1660 1665
Ile Asn Leu Leu Arg Pro Leu Leu Trp Asp Tyr Ile Cys Ile Ser
1670 1675 1680
Leu Ser Asn Ser Phe Glu Leu Gly Val Trp Val Leu Ala Glu Pro
1685 1690 1695
Val Lys Gly Lys Asn Glu Ser Asn Ser Ala Val Arg His Leu Asn
1700 1705 1710
Pro Cys Asp Tyr Val Ala Arg Lys Pro Glu Ser Ser Arg Leu Leu
1715 1720 1725
Glu Asp Lys Val Ser Leu Asn His Val Ile Gln Ser Val Arg Arg
1730 1735 1740
Leu Tyr Pro Lys Ile Phe Glu Asp Gln Leu Leu Pro Phe Met Ser
1745 1750 1755
Asp Val Ser Ser Lys Asn Met Arg Trp Ser Pro Arg Ile Lys Phe
1760 1765 1770
Leu Asp Leu Cys Val Leu Ile Asp Ile Asn Ser Glu Ser Leu Ser
1775 1780 1785
Leu Ile Ser His Val Val Lys Trp Lys Arg Asp Glu His Tyr Thr
1790 1795 1800
Val Leu Phe Ser Asp Leu Val Asn Ser His Gln Arg Ser Asp Ser
1805 1810 1815
Ser Leu Val Asp Glu Phe Val Val Ser Thr Arg Asp Val Cys Lys
1820 1825 1830
Asn Phe Leu Lys Gln Val Tyr Phe Glu Ser Phe Val Arg Glu Phe
1835 1840 1845
Val Ala Thr Ala Arg Thr Leu Gly Asn Phe Ser Trp Phe Pro His
1850 1855 1860
Lys Asp Met Met Pro Ser Glu Asp Gly Ala Glu Ala Leu Gly Pro
1865 1870 1875
Phe Gln Ser Phe Ile Leu Lys Val Val Asn Lys Lys Ile Glu Arg
1880 1885 1890
Pro Met Phe Arg Asn Asp Leu Gln Phe Gly Phe Gly Trp Phe Ser
1895 1900 1905
Tyr Arg Val Gly Asp Val Val Cys Asn Ala Ala Met Leu Ile Lys
1910 1915 1920
Gln Gly Leu Thr Asp Pro Lys Ala Phe Lys Ser Leu Arg Asp Leu
1925 1930 1935
Trp Asp Tyr Met Leu Ser Ser Thr Glu Gly Ile Leu Glu Phe Ser
1940 1945 1950
Ile Thr Val Asp Phe Thr His Asn Gln Asn Asn Thr Asp Cys Leu
1955 1960 1965
Arg Lys Phe Ser Leu Ile Phe Val Val Lys Cys Gln Leu Gln Ser
1970 1975 1980
Pro Gly Val Ala Asp Tyr Leu Ser Cys Ser His Ser Phe Lys Gly
1985 1990 1995
Glu Val Asp Arg Arg Leu Leu Asp Glu Cys Leu Asn Leu Leu Arg
2000 2005 2010
Thr Asp Pro Ile Phe Lys Ala Asn Asp Gly Val Phe Asp Ile Arg
2015 2020 2025
Ser Glu Glu Phe Glu Asp Tyr Met Glu Asp Pro Leu Thr Leu Gly
2030 2035 2040
Asp Ser Leu Glu Leu Glu Leu Ile Gly Ser Arg Arg Ile Leu Asn
2045 2050 2055
Glu Ile Lys Ser Thr Asp Phe Glu Arg Ile Gly Pro Glu Trp Glu
2060 2065 2070
Pro Val Pro Leu Thr Ile Arg Lys Gly Ala Leu Phe Glu Gly Arg
2075 2080 2085
Asn Phe Val Gln Asn Ile Ser Val Lys Leu Glu Thr Lys Asp Met
2090 2095 2100
Arg Val Phe Leu Ala Glu Leu Glu Gly Cys Gly Lys Ile Gly Asp
2105 2110 2115
Val Leu Gly Ser Leu Leu Leu His Arg Phe Arg Thr Gly Glu His
2120 2125 2130
Leu Met Glu Ser Glu Ile Ser Thr Val Leu Gln Glu Leu Cys Met
2135 2140 2145
Asp Arg Ser Val Met Leu Thr Pro Leu Ser Phe Val Pro Asp Trp
2150 2155 2160
Phe Thr Phe Arg Asp Cys Arg Leu Cys Phe Ser Xaa Ser Lys Asn
2165 2170 2175
Thr Val Met Tyr Glu Thr Thr Gly Gly Arg Phe Arg Leu Lys Gly
2180 2185 2190
Lys Ser Cys Asp Asp Trp Leu Ala Glu Arg Val Ala Glu Glu Ile
2195 2200 2205
Asp
<210> 41
<211> 1497
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-1)
<400> 41
atgggtcaga ttgtgacaat gtttgaggct ttgcctcaca tcattgatga ggtcatcaac 60
attgtcatta ttgtgctcat tataatcacg agcatcaaag ctgtgtacaa tttcgccacc 120
tgtgggatat tagcactggt cagcttcctt tttttggctg gtaggtcctg tggcatgtac 180
ggcctcaatg gtcccgacat ctataaaggg gtttaccagt tcaaatcagt ggagtttgat 240
atgtctcact taaatctgac gatgcccaat gcgtgctcag ccaacaactc tcatcactac 300
atcagtatgg gaagctctgg actggagcta actttcacta acgactccat ccttaatcac 360
aatttttgca acttaacctc cgctttcaac aaaaagactt ttgaccatac actcatgagt 420
atagtctcga gtctgcacct cagtattaga gggaattcca accacaaagc agtgtcttgt 480
gattttaaca atggcatcac cattcaatac aacttgtcat tttcggaccc acagagcgct 540
atgagccagt gttggacttt cagaggtaga gtcttggaca tgtttagaac tgcctttgga 600
ggaaaataca tgagaagtgg ctggggctgg gcaggttcag atggcaagac cacttggtgc 660
agccaaacaa gctatcagta cctaatcata caaaacagga cttgggaaaa ccactgtaga 720
tatgcaggcc cttttgggat gtctagaatc ctctttgctc aggaaaagac aaagtttctc 780
actaggagac ttgcaggcac attcacctgg accctgtcag actcctcagg agtagaaaat 840
ccaggtggtt attgcctgac caaatggatg atccttgctg cagagctcaa atgttttggg 900
aatacagctg ttgcaaaatg taatgtcaat catgatgaag agttctgtga catgctacga 960
ctaattgatt acaacaaggc cgccctgagt aagttcaagc aagatgtaga gtctgccttg 1020
catgtattca aaacaacagt aaattctctg atttccgatc agctgttgat gaggaatcat 1080
ctaagagatc taatgggggt accatactgt aattactcaa agttctggta tctggaacat 1140
gctaagactg gtgagactag tgtacccaag tgctggcttg tcactaatgg ctcctacttg 1200
aatgagaccc actttagtga tcaaatcgaa caagaagcag ataacatgat cacagagatg 1260
ttgaggaagg actacataaa aagacaaggg agtactcctt tagccttaat ggatcttttg 1320
atgttttcaa catcagcata tctaatcagc atctttctgc atcttgtgaa gataccaaca 1380
catagacaca taaagggcgg ttcatgtcca aagccacacc gcttgaccaa caaggggatc 1440
tgtagttgtg gtgcattcaa ggtgcctggt gtaaaaacta tctggaaaag acgctga 1497
<210> 42
<211> 498
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-1)
<400> 42
Met Gly Gln Ile Val Thr Met Phe Glu Ala Leu Pro His Ile Ile Asp
1 5 10 15
Glu Val Ile Asn Ile Val Ile Ile Val Leu Ile Ile Ile Thr Ser Ile
20 25 30
Lys Ala Val Tyr Asn Phe Ala Thr Cys Gly Ile Leu Ala Leu Val Ser
35 40 45
Phe Leu Phe Leu Ala Gly Arg Ser Cys Gly Met Tyr Gly Leu Asn Gly
50 55 60
Pro Asp Ile Tyr Lys Gly Val Tyr Gln Phe Lys Ser Val Glu Phe Asp
65 70 75 80
Met Ser His Leu Asn Leu Thr Met Pro Asn Ala Cys Ser Ala Asn Asn
85 90 95
Ser His His Tyr Ile Ser Met Gly Ser Ser Gly Leu Glu Leu Thr Phe
100 105 110
Thr Asn Asp Ser Ile Leu Asn His Asn Phe Cys Asn Leu Thr Ser Ala
115 120 125
Phe Asn Lys Lys Thr Phe Asp His Thr Leu Met Ser Ile Val Ser Ser
130 135 140
Leu His Leu Ser Ile Arg Gly Asn Ser Asn His Lys Ala Val Ser Cys
145 150 155 160
Asp Phe Asn Asn Gly Ile Thr Ile Gln Tyr Asn Leu Ser Phe Ser Asp
165 170 175
Pro Gln Ser Ala Met Ser Gln Cys Trp Thr Phe Arg Gly Arg Val Leu
180 185 190
Asp Met Phe Arg Thr Ala Phe Gly Gly Lys Tyr Met Arg Ser Gly Trp
195 200 205
Gly Trp Ala Gly Ser Asp Gly Lys Thr Thr Trp Cys Ser Gln Thr Ser
210 215 220
Tyr Gln Tyr Leu Ile Ile Gln Asn Arg Thr Trp Glu Asn His Cys Arg
225 230 235 240
Tyr Ala Gly Pro Phe Gly Met Ser Arg Ile Leu Phe Ala Gln Glu Lys
245 250 255
Thr Lys Phe Leu Thr Arg Arg Leu Ala Gly Thr Phe Thr Trp Thr Leu
260 265 270
Ser Asp Ser Ser Gly Val Glu Asn Pro Gly Gly Tyr Cys Leu Thr Lys
275 280 285
Trp Met Ile Leu Ala Ala Glu Leu Lys Cys Phe Gly Asn Thr Ala Val
290 295 300
Ala Lys Cys Asn Val Asn His Asp Glu Glu Phe Cys Asp Met Leu Arg
305 310 315 320
Leu Ile Asp Tyr Asn Lys Ala Ala Leu Ser Lys Phe Lys Gln Asp Val
325 330 335
Glu Ser Ala Leu His Val Phe Lys Thr Thr Val Asn Ser Leu Ile Ser
340 345 350
Asp Gln Leu Leu Met Arg Asn His Leu Arg Asp Leu Met Gly Val Pro
355 360 365
Tyr Cys Asn Tyr Ser Lys Phe Trp Tyr Leu Glu His Ala Lys Thr Gly
370 375 380
Glu Thr Ser Val Pro Lys Cys Trp Leu Val Thr Asn Gly Ser Tyr Leu
385 390 395 400
Asn Glu Thr His Phe Ser Asp Gln Ile Glu Gln Glu Ala Asp Asn Met
405 410 415
Ile Thr Glu Met Leu Arg Lys Asp Tyr Ile Lys Arg Gln Gly Ser Thr
420 425 430
Pro Leu Ala Leu Met Asp Leu Leu Met Phe Ser Thr Ser Ala Tyr Leu
435 440 445
Ile Ser Ile Phe Leu His Leu Val Lys Ile Pro Thr His Arg His Ile
450 455 460
Lys Gly Gly Ser Cys Pro Lys Pro His Arg Leu Thr Asn Lys Gly Ile
465 470 475 480
Cys Ser Cys Gly Ala Phe Lys Val Pro Gly Val Lys Thr Ile Trp Lys
485 490 495
Arg Arg
<210> 43
<211> 1677
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-1)
<400> 43
atgtctttgt ccaaagaagt caaaagcttt cagtggacac aggcgttgag gagggagttg 60
cagagtttta catcagatgt aaaggctgcc gtcatcaagg acgcaaccag tcttctaaat 120
gggttggact tttctgaagt cagcaacgtt cagaggatca tgagaaagga aaggagggat 180
gataaagact tgcagagact caggagtctt aaccagactg tgcattctct tgttgatctg 240
aagtctacat caaagaaaaa tgttctgaaa gtgggaagac ttagtgcaga ggaattgatg 300
acccttgcag ctgatcttga gaagctgaag gccaaaatta tgagaactga gaggcctcaa 360
gcttctggag tctacatggg aaatttgaca gcacaacaac ttgatcaaag atcccaaata 420
ctgcaaatgg ttgggatgag aagacctcag cagggtgcaa gtggtgtagt aagggtttgg 480
gatgtgaagg actcatcact tctgaacaat cagttcggca caatgccaag cctgacaatg 540
gcttgcatgg caaaacagtc acagacccca ctcaatgatg ttgtgcaggc actcacagac 600
cttggcttac tttacacagt caaatacccg aatctcagtg atcttgaaag gctaaaggat 660
aaacacccag ttctgggggt cattactgaa cagcaatcta gtatcaatat ctctggttat 720
aatttcagtc ttggtgcagc tgtgaaagcg ggggcagctc tgctagatgg agggaacatg 780
ctggaatcta tcttgatcaa accgagcaac agtgaggatc tcctaaaagc agtcctcggg 840
gccaagaaga aactcaacat gtttgtctca gatcaagttg gagatagaaa tccctatgaa 900
aacatccttt ataaagtctg tctttcaggt gaaggatggc catacatagc ctgtagaacg 960
tcagttgtgg ggagagcatg ggagaacaca acaattgatc tcacaaatga aaaacttgtt 1020
gccaactcat ctaggccagt gcctggagca gcaggcccac ctcaggtggg cttgagttac 1080
agtcagacaa tgctgttgaa agacttgatg ggagggattg atcccaatgc tcccacatgg 1140
attgacattg agggcaggtt caatgatcca gtggagatag caatattcca accacaaaat 1200
gggcaattca tacattttta cagggaacct acggaccaga agcaattcaa gcaggactca 1260
aagtattcac acggcatgga tcttgctgat ctcttcaatg cacagcctgg gctgacctca 1320
tcagttatag gtgctctccc acaagggatg gttttgagct gtcaaggttc tgatgacatc 1380
agaaagcttc tggactcaca aaatagaagg gacataaaac tcattgatgt tgagatgacc 1440
aaggaggcct caagagaata tgaagataaa gtgtgggaca aatatggctg gctatgcaaa 1500
atgcacactg gggtagtgag agacaaaaag aagaaagaga tcaccccaca ctgtgcactc 1560
atggactgca tcatttttga gagtgcttcc aaggcaagac tccctgatct aaaaaccgtt 1620
cacaacatcc tgccacatga tttaatcttc agaggaccca atgttgtgac actctaa 1677
<210> 44
<211> 558
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-1)
<400> 44
Met Ser Leu Ser Lys Glu Val Lys Ser Phe Gln Trp Thr Gln Ala Leu
1 5 10 15
Arg Arg Glu Leu Gln Ser Phe Thr Ser Asp Val Lys Ala Ala Val Ile
20 25 30
Lys Asp Ala Thr Ser Leu Leu Asn Gly Leu Asp Phe Ser Glu Val Ser
35 40 45
Asn Val Gln Arg Ile Met Arg Lys Glu Arg Arg Asp Asp Lys Asp Leu
50 55 60
Gln Arg Leu Arg Ser Leu Asn Gln Thr Val His Ser Leu Val Asp Leu
65 70 75 80
Lys Ser Thr Ser Lys Lys Asn Val Leu Lys Val Gly Arg Leu Ser Ala
85 90 95
Glu Glu Leu Met Thr Leu Ala Ala Asp Leu Glu Lys Leu Lys Ala Lys
100 105 110
Ile Met Arg Thr Glu Arg Pro Gln Ala Ser Gly Val Tyr Met Gly Asn
115 120 125
Leu Thr Ala Gln Gln Leu Asp Gln Arg Ser Gln Ile Leu Gln Met Val
130 135 140
Gly Met Arg Arg Pro Gln Gln Gly Ala Ser Gly Val Val Arg Val Trp
145 150 155 160
Asp Val Lys Asp Ser Ser Leu Leu Asn Asn Gln Phe Gly Thr Met Pro
165 170 175
Ser Leu Thr Met Ala Cys Met Ala Lys Gln Ser Gln Thr Pro Leu Asn
180 185 190
Asp Val Val Gln Ala Leu Thr Asp Leu Gly Leu Leu Tyr Thr Val Lys
195 200 205
Tyr Pro Asn Leu Ser Asp Leu Glu Arg Leu Lys Asp Lys His Pro Val
210 215 220
Leu Gly Val Ile Thr Glu Gln Gln Ser Ser Ile Asn Ile Ser Gly Tyr
225 230 235 240
Asn Phe Ser Leu Gly Ala Ala Val Lys Ala Gly Ala Ala Leu Leu Asp
245 250 255
Gly Gly Asn Met Leu Glu Ser Ile Leu Ile Lys Pro Ser Asn Ser Glu
260 265 270
Asp Leu Leu Lys Ala Val Leu Gly Ala Lys Lys Lys Leu Asn Met Phe
275 280 285
Val Ser Asp Gln Val Gly Asp Arg Asn Pro Tyr Glu Asn Ile Leu Tyr
290 295 300
Lys Val Cys Leu Ser Gly Glu Gly Trp Pro Tyr Ile Ala Cys Arg Thr
305 310 315 320
Ser Val Val Gly Arg Ala Trp Glu Asn Thr Thr Ile Asp Leu Thr Asn
325 330 335
Glu Lys Leu Val Ala Asn Ser Ser Arg Pro Val Pro Gly Ala Ala Gly
340 345 350
Pro Pro Gln Val Gly Leu Ser Tyr Ser Gln Thr Met Leu Leu Lys Asp
355 360 365
Leu Met Gly Gly Ile Asp Pro Asn Ala Pro Thr Trp Ile Asp Ile Glu
370 375 380
Gly Arg Phe Asn Asp Pro Val Glu Ile Ala Ile Phe Gln Pro Gln Asn
385 390 395 400
Gly Gln Phe Ile His Phe Tyr Arg Glu Pro Thr Asp Gln Lys Gln Phe
405 410 415
Lys Gln Asp Ser Lys Tyr Ser His Gly Met Asp Leu Ala Asp Leu Phe
420 425 430
Asn Ala Gln Pro Gly Leu Thr Ser Ser Val Ile Gly Ala Leu Pro Gln
435 440 445
Gly Met Val Leu Ser Cys Gln Gly Ser Asp Asp Ile Arg Lys Leu Leu
450 455 460
Asp Ser Gln Asn Arg Arg Asp Ile Lys Leu Ile Asp Val Glu Met Thr
465 470 475 480
Lys Glu Ala Ser Arg Glu Tyr Glu Asp Lys Val Trp Asp Lys Tyr Gly
485 490 495
Trp Leu Cys Lys Met His Thr Gly Val Val Arg Asp Lys Lys Lys Lys
500 505 510
Glu Ile Thr Pro His Cys Ala Leu Met Asp Cys Ile Ile Phe Glu Ser
515 520 525
Ala Ser Lys Ala Arg Leu Pro Asp Leu Lys Thr Val His Asn Ile Leu
530 535 540
Pro His Asp Leu Ile Phe Arg Gly Pro Asn Val Val Thr Leu
545 550 555
<210> 45
<211> 273
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-1)
<400> 45
atgggccaag gcaagtccaa agaagaaagg gacaccagca atacaggcag agcagagctt 60
ttgccagaca ccacctatct tggtcctcta aattgtaaat catgttggca gaaatttgac 120
agcttggtta gatgccatga ccactatctt tgcagacact gtctgaatct cctgctgtca 180
gtttccgaca gatgtcctct ctgtaagtat ccactgccaa ccaaactgaa ggtgtcaaca 240
gtcccaagct ccccacctcc ctatgaggag tga 273
<210> 46
<211> 90
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-1)
<400> 46
Met Gly Gln Gly Lys Ser Lys Glu Glu Arg Asp Thr Ser Asn Thr Gly
1 5 10 15
Arg Ala Glu Leu Leu Pro Asp Thr Thr Tyr Leu Gly Pro Leu Asn Cys
20 25 30
Lys Ser Cys Trp Gln Lys Phe Asp Ser Leu Val Arg Cys His Asp His
35 40 45
Tyr Leu Cys Arg His Cys Leu Asn Leu Leu Leu Ser Val Ser Asp Arg
50 55 60
Cys Pro Leu Cys Lys Tyr Pro Leu Pro Thr Lys Leu Lys Val Ser Thr
65 70 75 80
Val Pro Ser Ser Pro Pro Pro Tyr Glu Glu
85 90
<210> 47
<211> 6630
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-1)
<400> 47
atggatgaaa ctattgcaga tttgagagag ttgtgtctaa attacataga acaggacgag 60
aggctgtcaa ggcaaaaact caacttcctg ggacaaagag aacccagaat ggtgctaatt 120
gagggactca aattgttatc acgctgtata gagatagaca gtgcagacaa aagtggttgc 180
atacacaacc acgatgacaa atctgttgaa acaatcctaa tagactctgg gattgtgtgt 240
ccaggactgc cactcatcat ccctgatggt tataagttga ttgacaattc ccttattctt 300
cttgaatgtt ttgttagaag cacaccagct agttttgaaa agaagttcat tgaggacacc 360
aacaaactag catgcatcaa agaagatctt gctgttgcag gcatcacact ggttccaata 420
gtggatggtc gttgtgatta tgataacagt ttcatgccag aatgggtgaa ttttaagttc 480
agagacctcc tatttaaact cctggagtat tctagtcaag atgagaaagt ttttgaggag 540
tctgaatact tcaggctctg tgagtctctt aagaccactg ttgacaaacg ttccggcatg 600
gactcaatga aaattttgaa agacgcaaga tcatttcata acgatgagat tatgaaaatg 660
tgccacgatg gtgtcaaccc caacatgagt tgcgatgatg tggtctttgg cataaattcc 720
ttttttggca ggtttaggag ggacctgtta aatgggagac tcaaaaggaa tttccaaaag 780
gtcagccctg ggggcttaat caaggaattc tctgaacttt atgaaaccct tactgataat 840
gatgacatat taatgttgag caaagaggca gttgaatcct gccccttaat gaggttcatt 900
acagcagaga cccatgggca tgagagagga agcgatgcta acactgagta tgaaaggcta 960
ctctctatgt tgaacaaggt gaaaagttta aaattattaa acactagaag gagacagctg 1020
ctgaacttag atgtcttatg tctttcttca cttattaagc agtcaatttc caaagggttg 1080
gaaaatgata aacattgggt tggttgttgc tacagtagtg tgaatgatag gcttgtgagc 1140
cttcaaagta ccaaagaaga attcatgaga cttttgaaga acagaagaaa atcaagagtg 1200
cacaaaaagg catctcttga tgagcttttt agggtatcca taaatgagtt catagcaaaa 1260
atccagaaat gcctatcaac agtgggactt agttttgagc attacggact atcagaatgc 1320
ctcgtgcaag aatgccatat accatttgct gaatttgaga actttatgag agccgggact 1380
catcctgtaa tgcattacac aaaatttgaa gattacactt tccagcctaa catagagcaa 1440
ttgaggggtt tacagagttt gagaaaactg tcatctgttt gtttggctct aacaaacagc 1500
atgaaaacaa gctcagttgc aaggttgaga cagaaccaac tggggtctgt gagatatcaa 1560
gtggtggagt gcaaagaggt gttttgccag ataataaaac tggattccga agagtatcat 1620
ctactatatc agaaaactgg agaatcatcg aggtgttatt ccatacaagg tccggatggt 1680
cacttgattt ccttttacgc agatccaaaa aggttctttt taccaatttt ttcagatgag 1740
gtgttgcaca acatgataga cacaatgatt tcatggatta ggtcatgccc tgacttaaaa 1800
gattctctta ttgacattga gactgcacta aggacattga tcctactgat gctcaccaac 1860
ccaacaaaga gaaatcaaaa gcaggttcaa aatattaggt atttagtgat ggccatcgtc 1920
tcagactttt catcgacctc attaatggat aagttgaagg aggatctaat cacacctgcc 1980
gagaaagtgg tgtacaggct gcttcggttt ttgattagga caatttttgg tactggtgaa 2040
aaggtgttat tgagtgcaaa attcaagttt atgttgaatg tgtcatacct gtgtcatttg 2100
atcacaaagg agacccctga tagattgaca gatcagataa aatgttttga aaagttcttt 2160
gagcccaaga gtgagtttgg tttctttgtc aaccctaagg aaacaatcac acccgaagag 2220
gaatgtgttt tttatgaaca aatgaagaag ttcaccggta aagatattga ttgtcagcat 2280
tcaacccctg gtgttaattt agagatcttt agcatgatgg tatcttcatt caacaatggc 2340
accttaattc taaaagggga gaaaaggctc aacaatctgg accccatgac caactctgga 2400
tgtgcgacag cattagatct cgcaagcaac aaaagtgtgg ttgtcaataa acatctgaat 2460
ggagaacggc ttttggagta tgattttaac aaattgcttg ttagtgctgt gagccaaatt 2520
acagagggct tcatgaggaa acaaaagtat aagctgagac actcagatta cgaatataag 2580
gtctcaaagc ttgtctctag attagtcatc ggttctagga aaacagaagt agacaaattg 2640
gaagatgatc cggtagatgt gtgtttcgag ggggaggagg agacaagttt tttcaggagt 2700
ttagaagata aggtcagctc cacaataaca cggtataata gaggcactag gcttaatgaa 2760
gggcaagggg agggagaatt caagaacaca aaaggactac accaccttca gattattttg 2820
tcaggtaaaa gagcttatct gaggaaagtc attttatcag aaatttcatt tcatctagta 2880
gaggactttg atccatcctg tctcaccaat gacgacatga ggtttatttg tgaggctgtt 2940
gaaggttcaa cagaactgtc accattgtat tttacatcag ctgtcaaaga acaatgtggt 3000
ctggatgaga tggcaagaaa cctctgtaga aagttcttct cagagggtga ttggttctca 3060
tgtatgaaga tgatcttgtt acagatgaat gcaaatgcgt attcagggaa gtacagacac 3120
atgcagaggc agagtttaaa ttttaaattt gactgggaca aattggaaga agatgtaaga 3180
attagtgaaa gggaaagcaa ttctgaatct ctaagtaagg ccctttcatt gacaaaatgc 3240
atgagtgctg ctctaaagaa tctgtgtttt tactcagaag aatcaccaac atcatacact 3300
tcagttggcc ctgactctgg gagactaaaa tttgcattgt catacaaaga gcaggttggg 3360
ggaaatagag agctttacat tggggatttg aggacaaaaa tgttcacaag attggtagaa 3420
gattattttg aatccttttc tagtttcttt tcaggatctt gtttaaacaa tgacaaagag 3480
tttgaaaatg caatcttgtc aatgactatc aatgtgagag aagggttgtt aaactacagc 3540
atggatcaca gcaaatgggg accaatgatg tgcccattcc tattcttaat gcttctccaa 3600
aatctcaaac tgggtgatga tcagtacgtg cgttctggga aagatcatgt tagcaccttg 3660
ttgacttggc atatgcataa acttgttgaa gtccctttcc ctgttgtgaa tgcaatgatg 3720
aaatcatatg ttaaatcaaa actcaagctt ctcaaagggt caggaacgac tgttacggag 3780
agaatcttta gagagtattt tgaaatgggg gtggtgccat ctcacatatc tagtctcatt 3840
gacatgggac aggggatcct acacaatgct tctgattttt acggtttaat tagtgaaagg 3900
tttatcaatt attgtattgg tgtcattttt ggagagaggc cagaagccta tacatcaagt 3960
gatgatcaga tcactttatt tgacaagaga ttgagtgact tagttgatag tgacccagaa 4020
gaagtccttg tcttgctgga attccactct cacttaagtg gtttgttgaa caagttcatc 4080
agtccaaaaa gtgtggttgg gcggtttgca gcggaattca aatccagatt ttatgtgtgg 4140
ggggaggagg tccctctcct cacgaaattt gtgtctgcgg cactacacaa tgttaagtgt 4200
aaagaaccgc atcaactttg tgagacaata gatacgattg ctgatcaagc tatagcaaat 4260
ggagttccag tttttttagt aaactgtatc cagaggagga cactggatct cttgaaatat 4320
gctaatttcc ctttagatcc attcttgtta aacactcaca ctgatgtaaa ggattggtta 4380
gatggttcta gaggttatag aatccaaaga ctcattgaag aattgtgtcc cagtgaaaca 4440
aagatcatga gaaaacttgt aagaagacta catcacaaac tcaagaacgg tgaatgtaac 4500
gaggaatttt ttctagacct cttcaacagg gaaatgaaag aggccatcct tcaattggga 4560
gagattcttg gtcttgagga tgatctcaat gagttggcaa gcatcaattg gttgaatctg 4620
aatgaaatgt tcccattgag gatggttctg agacaaaaag tggtttaccc atcagtaatg 4680
acctttcaag aggaaaagat cccctcattg attaaaacac tccaaaataa gctttgtagt 4740
aagttcacaa gaggtgcaca gaagctgttg tcagaggcaa tcaacaaatc agcttttcag 4800
agttgtgtct catccggctt tataggtctc tgtaagactt taggaagtag gtgtgtgaga 4860
aataaaaaca gggaaaatat gtatatcaga aaggtgcttg aagatctgac catggatgaa 4920
catgtcacaa gggttcacaa acaagatggt gtgatgttgt acatttgcga caagcagaga 4980
cacccagagg ctcaccgtga ccacatcaac cttttgaggc cccttctctg ggactacatt 5040
tgcatctcat tgagcaactc ttttgagctg ggtgtttggg ttttagcaga acctgtgaaa 5100
ggaaagaacg agagtaattc ggctgttagg cacttaaatc catgtgatta tgtagcaaga 5160
aaacctgaga gttcgagact actagaggat aaagtgagtt tgaatcatgt aattcaatct 5220
gtgaggcgac tgtaccccaa aatctttgag gatcagttgc tcccattcat gtctgatgtg 5280
agctcaaaaa atatgagatg gagtcccagg attaaattcc ttgacctttg tgtgctgatt 5340
gacatcaact cagagtcttt gtcactcatt tctcatgttg tcaaatggaa gagggacgaa 5400
cattacactg tgctgttttc tgatctcgtc aactctcacc aacggtcaga ctcaagttta 5460
gttgatgaat ttgttgtcag cacaagggat gtctgcaaga actttttgaa gcaagtgtat 5520
ttcgaatcat ttgtacgaga gtttgttgca acagctagga ccttaggtaa cttttcatgg 5580
ttcccccata aggacatgat gccatctgaa gatggcgctg aagcactggg acccttccaa 5640
tcatttattt tgaaagtggt gaacaagaaa atagagaggc ccatgtttag gaatgacttg 5700
cagtttggtt ttggttggtt ctcttatcgt gtgggggatg ttgtgtgtaa tgccgctatg 5760
ttaattaagc agggtttgac agatccaaaa gcatttaaat ctttaagaga tttgtgggat 5820
tacatgctca gcagcacaga ggggatattg gagttctcaa tcacagtgga tttcacacac 5880
aaccagaaca acactgactg cttgaggaaa ttttcattga tctttgtggt taaatgccaa 5940
ttacagagtc caggtgtagc tgattactta tcgtgctctc atttcttcaa aggtgaggtt 6000
gacaggagat tattagatga gtgtctcaat ctgttgagga cagaccccat ctttaaagcg 6060
aatgatggag tctttgacat taggtctgaa gagtttgaag attacatgga agaccctttg 6120
acacttggtg attcactaga acttgaacta ataggttcta gaaggattct gaatgagatc 6180
aaatctactg actttgagag gatagggcct gagtgggaac ctgtgcctct gaccataagg 6240
aagggtgccc tctttgaggg gaggaacttt gttcagaata tctctgtgaa attggagaca 6300
aaggacatga gggtctttct ggcagagctc gagggctgtg gagaaattgg tgatgtcctc 6360
ggcagcctcc tcctgcaccg attcagaact ggtgagcact tgatggagtc agaaataagt 6420
rcagttcttc aggagctctg catggacaga tccgtcatgc tgacaccatt atcttttgtg 6480
ccagattggt tcaccttcag agattgtagg ctctgcttca gcaggtcaaa gaacactgta 6540
atgtatgaga cagctggggg caggttcaga ctcaagggga aatcctgtga cgattggctg 6600
gcggagcggg tggccgagga gatcgactag 6630
<210> 48
<211> 2209
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-1)
<400> 48
Met Asp Glu Thr Ile Ala Asp Leu Arg Glu Leu Cys Leu Asn Tyr Ile
1 5 10 15
Glu Gln Asp Glu Arg Leu Ser Arg Gln Lys Leu Asn Phe Leu Gly Gln
20 25 30
Arg Glu Pro Arg Met Val Leu Ile Glu Gly Leu Lys Leu Leu Ser Arg
35 40 45
Cys Ile Glu Ile Asp Ser Ala Asp Lys Ser Gly Cys Ile His Asn His
50 55 60
Asp Asp Lys Ser Val Glu Thr Ile Leu Ile Asp Ser Gly Ile Val Cys
65 70 75 80
Pro Gly Leu Pro Leu Ile Ile Pro Asp Gly Tyr Lys Leu Ile Asp Asn
85 90 95
Ser Leu Ile Leu Leu Glu Cys Phe Val Arg Ser Thr Pro Ala Ser Phe
100 105 110
Glu Lys Lys Phe Ile Glu Asp Thr Asn Lys Leu Ala Cys Ile Lys Glu
115 120 125
Asp Leu Ala Val Ala Gly Ile Thr Leu Val Pro Ile Val Asp Gly Arg
130 135 140
Cys Asp Tyr Asp Asn Ser Phe Met Pro Glu Trp Val Asn Phe Lys Phe
145 150 155 160
Arg Asp Leu Leu Phe Lys Leu Leu Glu Tyr Ser Ser Gln Asp Glu Lys
165 170 175
Val Phe Glu Glu Ser Glu Tyr Phe Arg Leu Cys Glu Ser Leu Lys Thr
180 185 190
Thr Val Asp Lys Arg Ser Gly Met Asp Ser Met Lys Ile Leu Lys Asp
195 200 205
Ala Arg Ser Phe His Asn Asp Glu Ile Met Lys Met Cys His Asp Gly
210 215 220
Val Asn Pro Asn Met Ser Cys Asp Asp Val Val Phe Gly Ile Asn Ser
225 230 235 240
Phe Phe Gly Arg Phe Arg Arg Asp Leu Leu Asn Gly Arg Leu Lys Arg
245 250 255
Asn Phe Gln Lys Val Ser Pro Gly Gly Leu Ile Lys Glu Phe Ser Glu
260 265 270
Leu Tyr Glu Thr Leu Thr Asp Asn Asp Asp Ile Leu Met Leu Ser Lys
275 280 285
Glu Ala Val Glu Ser Cys Pro Leu Met Arg Phe Ile Thr Ala Glu Thr
290 295 300
His Gly His Glu Arg Gly Ser Asp Ala Asn Thr Glu Tyr Glu Arg Leu
305 310 315 320
Leu Ser Met Leu Asn Lys Val Lys Ser Leu Lys Leu Leu Asn Thr Arg
325 330 335
Arg Arg Gln Leu Leu Asn Leu Asp Val Leu Cys Leu Ser Ser Leu Ile
340 345 350
Lys Gln Ser Ile Ser Lys Gly Leu Glu Asn Asp Lys His Trp Val Gly
355 360 365
Cys Cys Tyr Ser Ser Val Asn Asp Arg Leu Val Ser Leu Gln Ser Thr
370 375 380
Lys Glu Glu Phe Met Arg Leu Leu Lys Asn Arg Arg Lys Ser Arg Val
385 390 395 400
His Lys Lys Ala Ser Leu Asp Glu Leu Phe Arg Val Ser Ile Asn Glu
405 410 415
Phe Ile Ala Lys Ile Gln Lys Cys Leu Ser Thr Val Gly Leu Ser Phe
420 425 430
Glu His Tyr Gly Leu Ser Glu Cys Leu Val Gln Glu Cys His Ile Pro
435 440 445
Phe Ala Glu Phe Glu Asn Phe Met Arg Ala Gly Thr His Pro Val Met
450 455 460
His Tyr Thr Lys Phe Glu Asp Tyr Thr Phe Gln Pro Asn Ile Glu Gln
465 470 475 480
Leu Arg Gly Leu Gln Ser Leu Arg Lys Leu Ser Ser Val Cys Leu Ala
485 490 495
Leu Thr Asn Ser Met Lys Thr Ser Ser Val Ala Arg Leu Arg Gln Asn
500 505 510
Gln Leu Gly Ser Val Arg Tyr Gln Val Val Glu Cys Lys Glu Val Phe
515 520 525
Cys Gln Ile Ile Lys Leu Asp Ser Glu Glu Tyr His Leu Leu Tyr Gln
530 535 540
Lys Thr Gly Glu Ser Ser Arg Cys Tyr Ser Ile Gln Gly Pro Asp Gly
545 550 555 560
His Leu Ile Ser Phe Tyr Ala Asp Pro Lys Arg Phe Phe Leu Pro Ile
565 570 575
Phe Ser Asp Glu Val Leu His Asn Met Ile Asp Thr Met Ile Ser Trp
580 585 590
Ile Arg Ser Cys Pro Asp Leu Lys Asp Ser Leu Ile Asp Ile Glu Thr
595 600 605
Ala Leu Arg Thr Leu Ile Leu Leu Met Leu Thr Asn Pro Thr Lys Arg
610 615 620
Asn Gln Lys Gln Val Gln Asn Ile Arg Tyr Leu Val Met Ala Ile Val
625 630 635 640
Ser Asp Phe Ser Ser Thr Ser Leu Met Asp Lys Leu Lys Glu Asp Leu
645 650 655
Ile Thr Pro Ala Glu Lys Val Val Tyr Arg Leu Leu Arg Phe Leu Ile
660 665 670
Arg Thr Ile Phe Gly Thr Gly Glu Lys Val Leu Leu Ser Ala Lys Phe
675 680 685
Lys Phe Met Leu Asn Val Ser Tyr Leu Cys His Leu Ile Thr Lys Glu
690 695 700
Thr Pro Asp Arg Leu Thr Asp Gln Ile Lys Cys Phe Glu Lys Phe Phe
705 710 715 720
Glu Pro Lys Ser Glu Phe Gly Phe Phe Val Asn Pro Lys Glu Thr Ile
725 730 735
Thr Pro Glu Glu Glu Cys Val Phe Tyr Glu Gln Met Lys Lys Phe Thr
740 745 750
Gly Lys Asp Ile Asp Cys Gln His Ser Thr Pro Gly Val Asn Leu Glu
755 760 765
Ile Phe Ser Met Met Val Ser Ser Phe Asn Asn Gly Thr Leu Ile Leu
770 775 780
Lys Gly Glu Lys Arg Leu Asn Asn Leu Asp Pro Met Thr Asn Ser Gly
785 790 795 800
Cys Ala Thr Ala Leu Asp Leu Ala Ser Asn Lys Ser Val Val Val Asn
805 810 815
Lys His Leu Asn Gly Glu Arg Leu Leu Glu Tyr Asp Phe Asn Lys Leu
820 825 830
Leu Val Ser Ala Val Ser Gln Ile Thr Glu Gly Phe Met Arg Lys Gln
835 840 845
Lys Tyr Lys Leu Arg His Ser Asp Tyr Glu Tyr Lys Val Ser Lys Leu
850 855 860
Val Ser Arg Leu Val Ile Gly Ser Arg Lys Thr Glu Val Asp Lys Leu
865 870 875 880
Glu Asp Asp Pro Val Asp Val Cys Phe Glu Gly Glu Glu Glu Thr Ser
885 890 895
Phe Phe Arg Ser Leu Glu Asp Lys Val Ser Ser Thr Ile Thr Arg Tyr
900 905 910
Asn Arg Gly Thr Arg Leu Asn Glu Gly Gln Gly Glu Gly Glu Phe Lys
915 920 925
Asn Thr Lys Gly Leu His His Leu Gln Ile Ile Leu Ser Gly Lys Arg
930 935 940
Ala Tyr Leu Arg Lys Val Ile Leu Ser Glu Ile Ser Phe His Leu Val
945 950 955 960
Glu Asp Phe Asp Pro Ser Cys Leu Thr Asn Asp Asp Met Arg Phe Ile
965 970 975
Cys Glu Ala Val Glu Gly Ser Thr Glu Leu Ser Pro Leu Tyr Phe Thr
980 985 990
Ser Ala Val Lys Glu Gln Cys Gly Leu Asp Glu Met Ala Arg Asn Leu
995 1000 1005
Cys Arg Lys Phe Phe Ser Glu Gly Asp Trp Phe Ser Cys Met Lys
1010 1015 1020
Met Ile Leu Leu Gln Met Asn Ala Asn Ala Tyr Ser Gly Lys Tyr
1025 1030 1035
Arg His Met Gln Arg Gln Ser Leu Asn Phe Lys Phe Asp Trp Asp
1040 1045 1050
Lys Leu Glu Glu Asp Val Arg Ile Ser Glu Arg Glu Ser Asn Ser
1055 1060 1065
Glu Ser Leu Ser Lys Ala Leu Ser Leu Thr Lys Cys Met Ser Ala
1070 1075 1080
Ala Leu Lys Asn Leu Cys Phe Tyr Ser Glu Glu Ser Pro Thr Ser
1085 1090 1095
Tyr Thr Ser Val Gly Pro Asp Ser Gly Arg Leu Lys Phe Ala Leu
1100 1105 1110
Ser Tyr Lys Glu Gln Val Gly Gly Asn Arg Glu Leu Tyr Ile Gly
1115 1120 1125
Asp Leu Arg Thr Lys Met Phe Thr Arg Leu Val Glu Asp Tyr Phe
1130 1135 1140
Glu Ser Phe Ser Ser Phe Phe Ser Gly Ser Cys Leu Asn Asn Asp
1145 1150 1155
Lys Glu Phe Glu Asn Ala Ile Leu Ser Met Thr Ile Asn Val Arg
1160 1165 1170
Glu Gly Leu Leu Asn Tyr Ser Met Asp His Ser Lys Trp Gly Pro
1175 1180 1185
Met Met Cys Pro Phe Leu Phe Leu Met Leu Leu Gln Asn Leu Lys
1190 1195 1200
Leu Gly Asp Asp Gln Tyr Val Arg Ser Gly Lys Asp His Val Ser
1205 1210 1215
Thr Leu Leu Thr Trp His Met His Lys Leu Val Glu Val Pro Phe
1220 1225 1230
Pro Val Val Asn Ala Met Met Lys Ser Tyr Val Lys Ser Lys Leu
1235 1240 1245
Lys Leu Leu Lys Gly Ser Gly Thr Thr Val Thr Glu Arg Ile Phe
1250 1255 1260
Arg Glu Tyr Phe Glu Met Gly Val Val Pro Ser His Ile Ser Ser
1265 1270 1275
Leu Ile Asp Met Gly Gln Gly Ile Leu His Asn Ala Ser Asp Phe
1280 1285 1290
Tyr Gly Leu Ile Ser Glu Arg Phe Ile Asn Tyr Cys Ile Gly Val
1295 1300 1305
Ile Phe Gly Glu Arg Pro Glu Ala Tyr Thr Ser Ser Asp Asp Gln
1310 1315 1320
Ile Thr Leu Phe Asp Lys Arg Leu Ser Asp Leu Val Asp Ser Asp
1325 1330 1335
Pro Glu Glu Val Leu Val Leu Leu Glu Phe His Ser His Leu Ser
1340 1345 1350
Gly Leu Leu Asn Lys Phe Ile Ser Pro Lys Ser Val Val Gly Arg
1355 1360 1365
Phe Ala Ala Glu Phe Lys Ser Arg Phe Tyr Val Trp Gly Glu Glu
1370 1375 1380
Val Pro Leu Leu Thr Lys Phe Val Ser Ala Ala Leu His Asn Val
1385 1390 1395
Lys Cys Lys Glu Pro His Gln Leu Cys Glu Thr Ile Asp Thr Ile
1400 1405 1410
Ala Asp Gln Ala Ile Ala Asn Gly Val Pro Val Phe Leu Val Asn
1415 1420 1425
Cys Ile Gln Arg Arg Thr Leu Asp Leu Leu Lys Tyr Ala Asn Phe
1430 1435 1440
Pro Leu Asp Pro Phe Leu Leu Asn Thr His Thr Asp Val Lys Asp
1445 1450 1455
Trp Leu Asp Gly Ser Arg Gly Tyr Arg Ile Gln Arg Leu Ile Glu
1460 1465 1470
Glu Leu Cys Pro Ser Glu Thr Lys Ile Met Arg Lys Leu Val Arg
1475 1480 1485
Arg Leu His His Lys Leu Lys Asn Gly Glu Cys Asn Glu Glu Phe
1490 1495 1500
Phe Leu Asp Leu Phe Asn Arg Glu Met Lys Glu Ala Ile Leu Gln
1505 1510 1515
Leu Gly Glu Ile Leu Gly Leu Glu Asp Asp Leu Asn Glu Leu Ala
1520 1525 1530
Ser Ile Asn Trp Leu Asn Leu Asn Glu Met Phe Pro Leu Arg Met
1535 1540 1545
Val Leu Arg Gln Lys Val Val Tyr Pro Ser Val Met Thr Phe Gln
1550 1555 1560
Glu Glu Lys Ile Pro Ser Leu Ile Lys Thr Leu Gln Asn Lys Leu
1565 1570 1575
Cys Ser Lys Phe Thr Arg Gly Ala Gln Lys Leu Leu Ser Glu Ala
1580 1585 1590
Ile Asn Lys Ser Ala Phe Gln Ser Cys Val Ser Ser Gly Phe Ile
1595 1600 1605
Gly Leu Cys Lys Thr Leu Gly Ser Arg Cys Val Arg Asn Lys Asn
1610 1615 1620
Arg Glu Asn Met Tyr Ile Arg Lys Val Leu Glu Asp Leu Thr Met
1625 1630 1635
Asp Glu His Val Thr Arg Val His Lys Gln Asp Gly Val Met Leu
1640 1645 1650
Tyr Ile Cys Asp Lys Gln Arg His Pro Glu Ala His Arg Asp His
1655 1660 1665
Ile Asn Leu Leu Arg Pro Leu Leu Trp Asp Tyr Ile Cys Ile Ser
1670 1675 1680
Leu Ser Asn Ser Phe Glu Leu Gly Val Trp Val Leu Ala Glu Pro
1685 1690 1695
Val Lys Gly Lys Asn Glu Ser Asn Ser Ala Val Arg His Leu Asn
1700 1705 1710
Pro Cys Asp Tyr Val Ala Arg Lys Pro Glu Ser Ser Arg Leu Leu
1715 1720 1725
Glu Asp Lys Val Ser Leu Asn His Val Ile Gln Ser Val Arg Arg
1730 1735 1740
Leu Tyr Pro Lys Ile Phe Glu Asp Gln Leu Leu Pro Phe Met Ser
1745 1750 1755
Asp Val Ser Ser Lys Asn Met Arg Trp Ser Pro Arg Ile Lys Phe
1760 1765 1770
Leu Asp Leu Cys Val Leu Ile Asp Ile Asn Ser Glu Ser Leu Ser
1775 1780 1785
Leu Ile Ser His Val Val Lys Trp Lys Arg Asp Glu His Tyr Thr
1790 1795 1800
Val Leu Phe Ser Asp Leu Val Asn Ser His Gln Arg Ser Asp Ser
1805 1810 1815
Ser Leu Val Asp Glu Phe Val Val Ser Thr Arg Asp Val Cys Lys
1820 1825 1830
Asn Phe Leu Lys Gln Val Tyr Phe Glu Ser Phe Val Arg Glu Phe
1835 1840 1845
Val Ala Thr Ala Arg Thr Leu Gly Asn Phe Ser Trp Phe Pro His
1850 1855 1860
Lys Asp Met Met Pro Ser Glu Asp Gly Ala Glu Ala Leu Gly Pro
1865 1870 1875
Phe Gln Ser Phe Ile Leu Lys Val Val Asn Lys Lys Ile Glu Arg
1880 1885 1890
Pro Met Phe Arg Asn Asp Leu Gln Phe Gly Phe Gly Trp Phe Ser
1895 1900 1905
Tyr Arg Val Gly Asp Val Val Cys Asn Ala Ala Met Leu Ile Lys
1910 1915 1920
Gln Gly Leu Thr Asp Pro Lys Ala Phe Lys Ser Leu Arg Asp Leu
1925 1930 1935
Trp Asp Tyr Met Leu Ser Ser Thr Glu Gly Ile Leu Glu Phe Ser
1940 1945 1950
Ile Thr Val Asp Phe Thr His Asn Gln Asn Asn Thr Asp Cys Leu
1955 1960 1965
Arg Lys Phe Ser Leu Ile Phe Val Val Lys Cys Gln Leu Gln Ser
1970 1975 1980
Pro Gly Val Ala Asp Tyr Leu Ser Cys Ser His Phe Phe Lys Gly
1985 1990 1995
Glu Val Asp Arg Arg Leu Leu Asp Glu Cys Leu Asn Leu Leu Arg
2000 2005 2010
Thr Asp Pro Ile Phe Lys Ala Asn Asp Gly Val Phe Asp Ile Arg
2015 2020 2025
Ser Glu Glu Phe Glu Asp Tyr Met Glu Asp Pro Leu Thr Leu Gly
2030 2035 2040
Asp Ser Leu Glu Leu Glu Leu Ile Gly Ser Arg Arg Ile Leu Asn
2045 2050 2055
Glu Ile Lys Ser Thr Asp Phe Glu Arg Ile Gly Pro Glu Trp Glu
2060 2065 2070
Pro Val Pro Leu Thr Ile Arg Lys Gly Ala Leu Phe Glu Gly Arg
2075 2080 2085
Asn Phe Val Gln Asn Ile Ser Val Lys Leu Glu Thr Lys Asp Met
2090 2095 2100
Arg Val Phe Leu Ala Glu Leu Glu Gly Cys Gly Glu Ile Gly Asp
2105 2110 2115
Val Leu Gly Ser Leu Leu Leu His Arg Phe Arg Thr Gly Glu His
2120 2125 2130
Leu Met Glu Ser Glu Ile Ser Thr Val Leu Gln Glu Leu Cys Met
2135 2140 2145
Asp Arg Ser Val Met Leu Thr Pro Leu Ser Phe Val Pro Asp Trp
2150 2155 2160
Phe Thr Phe Arg Asp Cys Arg Leu Cys Phe Ser Arg Ser Lys Asn
2165 2170 2175
Thr Val Met Tyr Glu Thr Ala Gly Gly Arg Phe Arg Leu Lys Gly
2180 2185 2190
Lys Ser Cys Asp Asp Trp Leu Ala Glu Arg Val Ala Glu Glu Ile
2195 2200 2205
Asp
<210> 49
<211> 1497
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-1.3)
<400> 49
atgggtcaga ttgtgacaat gtttgaggct ttgcctcaca tcattgatga ggtcatcaac 60
attgtcatta ttgtgctcat tataatcacg agcatcaaag ctgtgtacaa tttcgccacc 120
tgtgggatat tagcactggt cagcttcctt tttttggctg gtaggtcctg tggcatgtac 180
ggccttaatg gtcccgacat ctataaaggg gtttaccagt tcaaatcagt ggagtttgat 240
atgtctcact taaatctgac gatgcccaat gcgtgctcag ccaacaactc tcatcactac 300
atcagtatgg gaagctctgg actggagcta actttcacta acgactccat ccttaatcac 360
aatttttgca acttaacctc cgctttcaac aaaaagactt ttgaccatac actcatgagt 420
atagtctcga gtctgcacct cagtattaga gggaattcca accacaaagc agtgtcttgt 480
gattttaaca atggcatcac cattcaatac aacttgtcat tttcggaccc acagagcgct 540
ataagccagt gttggacttt cagaggtaga gtcttggaca tgtttagaac tgcctttgga 600
ggaaaataca tgagaagtgg ctggggctgg gcaggttcag atggcaagac cacttggtgc 660
agccaaacaa gctatcagta cctaatcata caaaacagga cttgggaaaa ccactgtaga 720
tatgcaggcc cttttgggat gtctagaatc ctctttgctc aggaaaagac aaagtttctc 780
actaggagac ttgcaggcac attcacctgg accctgtcag actcctcagg agtagaaaat 840
ccaggtggtt attgcctgac caaatggatg atccttgctg cagagctcaa atgttttggg 900
aacacagctg ttgcaaaatg taatgtcaat catgatgaag agttctgtga catgctacga 960
ctaattgatt acaacaaggc cgccctgagt aagttcaagc aagatgtaga gtctgccttg 1020
catgtattca aaacaacagt aaattctctg atttccgatc agctgttgat gaggaatcat 1080
ctaagagatc taatgggggt accatactgt aattactcaa agttctggta tctggaacat 1140
gctaagactg gtgagactag tgtacccaag tgctggcttg tcactaatgg ctcctacttg 1200
aatgagaccc actttagtga tcaaatcgaa caagaagcag ataacatgat cacagagatg 1260
ttgaggaagg actacataaa aagacaaggg agtactcctt tagccttaat ggatcttttg 1320
atgttttcaa catcagcata tctaatcagc atctttctgc atcttgtgaa gataccaaca 1380
catagacaca taaagggcgg ttcatgtcca aagccacacc gcttgaccaa caaggggatc 1440
tgtagttgtg gtgcattcaa ggtgcctggt gtaaaaacta tctggaaaag acgctga 1497
<210> 50
<211> 498
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-1.3)
<400> 50
Met Gly Gln Ile Val Thr Met Phe Glu Ala Leu Pro His Ile Ile Asp
1 5 10 15
Glu Val Ile Asn Ile Val Ile Ile Val Leu Ile Ile Ile Thr Ser Ile
20 25 30
Lys Ala Val Tyr Asn Phe Ala Thr Cys Gly Ile Leu Ala Leu Val Ser
35 40 45
Phe Leu Phe Leu Ala Gly Arg Ser Cys Gly Met Tyr Gly Leu Asn Gly
50 55 60
Pro Asp Ile Tyr Lys Gly Val Tyr Gln Phe Lys Ser Val Glu Phe Asp
65 70 75 80
Met Ser His Leu Asn Leu Thr Met Pro Asn Ala Cys Ser Ala Asn Asn
85 90 95
Ser His His Tyr Ile Ser Met Gly Ser Ser Gly Leu Glu Leu Thr Phe
100 105 110
Thr Asn Asp Ser Ile Leu Asn His Asn Phe Cys Asn Leu Thr Ser Ala
115 120 125
Phe Asn Lys Lys Thr Phe Asp His Thr Leu Met Ser Ile Val Ser Ser
130 135 140
Leu His Leu Ser Ile Arg Gly Asn Ser Asn His Lys Ala Val Ser Cys
145 150 155 160
Asp Phe Asn Asn Gly Ile Thr Ile Gln Tyr Asn Leu Ser Phe Ser Asp
165 170 175
Pro Gln Ser Ala Ile Ser Gln Cys Trp Thr Phe Arg Gly Arg Val Leu
180 185 190
Asp Met Phe Arg Thr Ala Phe Gly Gly Lys Tyr Met Arg Ser Gly Trp
195 200 205
Gly Trp Ala Gly Ser Asp Gly Lys Thr Thr Trp Cys Ser Gln Thr Ser
210 215 220
Tyr Gln Tyr Leu Ile Ile Gln Asn Arg Thr Trp Glu Asn His Cys Arg
225 230 235 240
Tyr Ala Gly Pro Phe Gly Met Ser Arg Ile Leu Phe Ala Gln Glu Lys
245 250 255
Thr Lys Phe Leu Thr Arg Arg Leu Ala Gly Thr Phe Thr Trp Thr Leu
260 265 270
Ser Asp Ser Ser Gly Val Glu Asn Pro Gly Gly Tyr Cys Leu Thr Lys
275 280 285
Trp Met Ile Leu Ala Ala Glu Leu Lys Cys Phe Gly Asn Thr Ala Val
290 295 300
Ala Lys Cys Asn Val Asn His Asp Glu Glu Phe Cys Asp Met Leu Arg
305 310 315 320
Leu Ile Asp Tyr Asn Lys Ala Ala Leu Ser Lys Phe Lys Gln Asp Val
325 330 335
Glu Ser Ala Leu His Val Phe Lys Thr Thr Val Asn Ser Leu Ile Ser
340 345 350
Asp Gln Leu Leu Met Arg Asn His Leu Arg Asp Leu Met Gly Val Pro
355 360 365
Tyr Cys Asn Tyr Ser Lys Phe Trp Tyr Leu Glu His Ala Lys Thr Gly
370 375 380
Glu Thr Ser Val Pro Lys Cys Trp Leu Val Thr Asn Gly Ser Tyr Leu
385 390 395 400
Asn Glu Thr His Phe Ser Asp Gln Ile Glu Gln Glu Ala Asp Asn Met
405 410 415
Ile Thr Glu Met Leu Arg Lys Asp Tyr Ile Lys Arg Gln Gly Ser Thr
420 425 430
Pro Leu Ala Leu Met Asp Leu Leu Met Phe Ser Thr Ser Ala Tyr Leu
435 440 445
Ile Ser Ile Phe Leu His Leu Val Lys Ile Pro Thr His Arg His Ile
450 455 460
Lys Gly Gly Ser Cys Pro Lys Pro His Arg Leu Thr Asn Lys Gly Ile
465 470 475 480
Cys Ser Cys Gly Ala Phe Lys Val Pro Gly Val Lys Thr Ile Trp Lys
485 490 495
Arg Arg
<210> 51
<211> 1677
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-1.3)
<400> 51
atgtctttgt ccaaagaagt caaaagcttt cagtggacac aggcgttgag gagggagttg 60
cagagtttta catcagatgt aaaggctgcc gtcatcaagg acgcaaccag tcttctaaat 120
gggttggact tttctgaagt cagcaacgtt cagaggatca tgagaaagga aaggagggat 180
gataaagact tgcagagact caggagtctt aaccagactg tgcattctct tgttgatctg 240
aagtctacat caaagaaaaa tgttctgaaa gtgggaagac ttagtgcaga ggaattgatg 300
acccttgcag ctgatctcga gaagctgaag gccaaaatta tgagaactga gaggcctcaa 360
gcttctggag tctacatggg aaatttgaca gcacaacaac ttgatcaaag atcccaaata 420
ctgcaaatgg ttgggatgag aagacctcag cagggtgcaa gtggtgtagt aagggtttgg 480
gatgtgaagg actcatcact tctgaacaat cagttcggca caatgccaag cctgacaatg 540
gcttgcatgg caaaacagtc acagacccca ctcaatgatg ttgtgcaggc actcacagac 600
cttggcttac tttacacagt caaatacccg aatctcagtg atcttgaaag gctaaaggat 660
aaacacccag ttctgggggt cattactgaa cagcaatcta gtatcaatat ctctggttat 720
aatttcagtc ttggtgcagc tgtgaaagcg ggggcagctc tgctagatgg agggaacatg 780
ctggaatcta tcttgatcaa accgagcaac agtgaggatc tcctaaaagc agtcctcggg 840
gccaagaaga aactcaacat gtttgtctca gatcaagttg gagatagaaa tccctatgaa 900
aacatccttt ataaagtctg tctttcaggt gaaggatggc catacatagc ctgtagaacg 960
tcagttgtgg ggagagcatg ggagaacaca acaattgatc tcacaaatga aaaacttgtt 1020
gccaactcat ctaggccagt gcctggagca gcaggcccac ctcaggtggg cttgagttac 1080
agtcagacaa tgctgttgaa agacttgatg ggagggattg atcccaatgc tcccacatgg 1140
attgacattg agggcaggtt caatgatcca gtggagatag caatattcca accacaaaat 1200
gggcaattca tacattttta cagggaacct acggaccaga agcaattcaa gcaggactca 1260
aagtattcac acggcatgga tcttgctgat ctcttcaatg cacagcctgg gctgacctca 1320
tcagttatag gtgctctccc acaagggatg gttttgagct gtcaaggttc tgatgacatc 1380
agaaagcttc tggactcaca aaatagaagg gacataaaac tcattgatgt tgagatgacc 1440
aaggaggcct caagagaata tgaagataaa gtgtgggaca aatatggctg gctatgcaaa 1500
atgcacactg gggtagtgag agacaaaaag aagaaagaga tcaccccaca ctgtgcactc 1560
atggactgca tcatttttga gagtgcttcc aaggcaagac tccctgatct aaaaaccgtt 1620
cacaacatcc tgccacatga tttaatcttc agaggaccca atgttgtgac actctaa 1677
<210> 52
<211> 558
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-1.3)
<400> 52
Met Ser Leu Ser Lys Glu Val Lys Ser Phe Gln Trp Thr Gln Ala Leu
1 5 10 15
Arg Arg Glu Leu Gln Ser Phe Thr Ser Asp Val Lys Ala Ala Val Ile
20 25 30
Lys Asp Ala Thr Ser Leu Leu Asn Gly Leu Asp Phe Ser Glu Val Ser
35 40 45
Asn Val Gln Arg Ile Met Arg Lys Glu Arg Arg Asp Asp Lys Asp Leu
50 55 60
Gln Arg Leu Arg Ser Leu Asn Gln Thr Val His Ser Leu Val Asp Leu
65 70 75 80
Lys Ser Thr Ser Lys Lys Asn Val Leu Lys Val Gly Arg Leu Ser Ala
85 90 95
Glu Glu Leu Met Thr Leu Ala Ala Asp Leu Glu Lys Leu Lys Ala Lys
100 105 110
Ile Met Arg Thr Glu Arg Pro Gln Ala Ser Gly Val Tyr Met Gly Asn
115 120 125
Leu Thr Ala Gln Gln Leu Asp Gln Arg Ser Gln Ile Leu Gln Met Val
130 135 140
Gly Met Arg Arg Pro Gln Gln Gly Ala Ser Gly Val Val Arg Val Trp
145 150 155 160
Asp Val Lys Asp Ser Ser Leu Leu Asn Asn Gln Phe Gly Thr Met Pro
165 170 175
Ser Leu Thr Met Ala Cys Met Ala Lys Gln Ser Gln Thr Pro Leu Asn
180 185 190
Asp Val Val Gln Ala Leu Thr Asp Leu Gly Leu Leu Tyr Thr Val Lys
195 200 205
Tyr Pro Asn Leu Ser Asp Leu Glu Arg Leu Lys Asp Lys His Pro Val
210 215 220
Leu Gly Val Ile Thr Glu Gln Gln Ser Ser Ile Asn Ile Ser Gly Tyr
225 230 235 240
Asn Phe Ser Leu Gly Ala Ala Val Lys Ala Gly Ala Ala Leu Leu Asp
245 250 255
Gly Gly Asn Met Leu Glu Ser Ile Leu Ile Lys Pro Ser Asn Ser Glu
260 265 270
Asp Leu Leu Lys Ala Val Leu Gly Ala Lys Lys Lys Leu Asn Met Phe
275 280 285
Val Ser Asp Gln Val Gly Asp Arg Asn Pro Tyr Glu Asn Ile Leu Tyr
290 295 300
Lys Val Cys Leu Ser Gly Glu Gly Trp Pro Tyr Ile Ala Cys Arg Thr
305 310 315 320
Ser Val Val Gly Arg Ala Trp Glu Asn Thr Thr Ile Asp Leu Thr Asn
325 330 335
Glu Lys Leu Val Ala Asn Ser Ser Arg Pro Val Pro Gly Ala Ala Gly
340 345 350
Pro Pro Gln Val Gly Leu Ser Tyr Ser Gln Thr Met Leu Leu Lys Asp
355 360 365
Leu Met Gly Gly Ile Asp Pro Asn Ala Pro Thr Trp Ile Asp Ile Glu
370 375 380
Gly Arg Phe Asn Asp Pro Val Glu Ile Ala Ile Phe Gln Pro Gln Asn
385 390 395 400
Gly Gln Phe Ile His Phe Tyr Arg Glu Pro Thr Asp Gln Lys Gln Phe
405 410 415
Lys Gln Asp Ser Lys Tyr Ser His Gly Met Asp Leu Ala Asp Leu Phe
420 425 430
Asn Ala Gln Pro Gly Leu Thr Ser Ser Val Ile Gly Ala Leu Pro Gln
435 440 445
Gly Met Val Leu Ser Cys Gln Gly Ser Asp Asp Ile Arg Lys Leu Leu
450 455 460
Asp Ser Gln Asn Arg Arg Asp Ile Lys Leu Ile Asp Val Glu Met Thr
465 470 475 480
Lys Glu Ala Ser Arg Glu Tyr Glu Asp Lys Val Trp Asp Lys Tyr Gly
485 490 495
Trp Leu Cys Lys Met His Thr Gly Val Val Arg Asp Lys Lys Lys Lys
500 505 510
Glu Ile Thr Pro His Cys Ala Leu Met Asp Cys Ile Ile Phe Glu Ser
515 520 525
Ala Ser Lys Ala Arg Leu Pro Asp Leu Lys Thr Val His Asn Ile Leu
530 535 540
Pro His Asp Leu Ile Phe Arg Gly Pro Asn Val Val Thr Leu
545 550 555
<210> 53
<211> 273
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-1.3)
<400> 53
atgggccaag gcaagtccaa agaagaaagg gacaccagca atacaggcag agcagagctt 60
ttgccagaca ccacctatct tggtcctcta aattgtaaat catgttggca gaaatttgac 120
agcttggtta gatgccatga ccactatctt tgcagacact gtctgaatct cctgctgtca 180
gtttccgaca gatgtcctct ctgtaagtat ccactgccaa ccaaactgaa ggtgtcaaca 240
gtcccaagct ccccacctcc ctatgaggag tga 273
<210> 54
<211> 90
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-1.3)
<400> 54
Met Gly Gln Gly Lys Ser Lys Glu Glu Arg Asp Thr Ser Asn Thr Gly
1 5 10 15
Arg Ala Glu Leu Leu Pro Asp Thr Thr Tyr Leu Gly Pro Leu Asn Cys
20 25 30
Lys Ser Cys Trp Gln Lys Phe Asp Ser Leu Val Arg Cys His Asp His
35 40 45
Tyr Leu Cys Arg His Cys Leu Asn Leu Leu Leu Ser Val Ser Asp Arg
50 55 60
Cys Pro Leu Cys Lys Tyr Pro Leu Pro Thr Lys Leu Lys Val Ser Thr
65 70 75 80
Val Pro Ser Ser Pro Pro Pro Tyr Glu Glu
85 90
<210> 55
<211> 6630
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-1.3)
<400> 55
atggatgaaa ctattgcaga tttgagagag ttgtgtctaa attacataga acaggacgag 60
aggctgtcaa ggcaaaaact caacttcctg ggacaaagag aacccagaat ggtgctaatt 120
gagggactca aattgttatc acgctgtata gagatagaca gtgcagacaa aagtggttgc 180
atacacaacc acgatgacaa atctgttgaa acaatcctaa tagactctgg gattgtgtgt 240
ccaggactgc cactcatcat ccctgatggt tataagttga ttgacaattc ccttattctt 300
cttgaatgtt ttgttagaag cacaccagct agttttgaaa agaagttcat tgaggacacc 360
aacaaactag catgcatcaa agaagatctt gctgttgcag gcatcacact ggttccaata 420
gtggatggtc gttgtgatta tgataacagt ttcatgccag aatgggtgaa ttttaagttc 480
agagacctcc tatttaaact cctggagtat tctagtcaag atgagaaagt ttttgaggag 540
tctgaatact tcaggctctg tgagtctctt aagaccactg ttgacaaacg ttccggcatg 600
gactcaatga aaattttgaa agacgcaaga tcatttcata acgatgagat tatgaaaatg 660
tgccacgatg gtgtcaaccc caacatgagt tgcgatgatg tggtctttgg cataaattcc 720
ttttttggca ggtttaggag ggacctgtta aatgggaaac tcaaaaggaa tttccaaaag 780
gtcagccctg ggggcttaat caaggaattc tctgaacttt atgaaaccct tactgataat 840
gatgacatat taatgttgag caaagaggca gttgaatcct gccccttaat gaggttcatt 900
acagcagaga cccatgggca tgagagagga agcgatgcta acactgagta tgaaaggcta 960
ctctctatgt taaacaaggt gaaaagttta aaattattaa acactagaag gagacagctg 1020
ctgaacttag atgtcttatg tctttcttca cttattaagc agtcaatttc caaagggttg 1080
gaaaatgata aacattgggt tggttgttgc tacagtagtg tgaatgatag gcttgtgagc 1140
cttcaaagta ccaaagaaga attcatgaga cttttgaaga acagaagaaa atcaagagtg 1200
cacaaaaagg catctcttga tgagcttttt agggtatcca taaatgagtt catagcaaaa 1260
atccagaaat gcctatcaac agtgggactt agttttgagc attacggact atcagaatgc 1320
ctcgtgcaag aatgccatat accatttgct gaatttgaga actttatgag agccgggact 1380
catcctgtaa tgcattacac aaaatttgaa gattacactt tccagcctaa catagagcaa 1440
ttgaggggtt tacagagttt gagaaaactg tcatctgttt gtttggctct aacaaacagc 1500
atgaaaacaa gctcagttgc aaggttgaga cagaaccaac tggggtctgt gagatatcaa 1560
gtggtggagt gcaaagaggt gttttgccag ataataaaac tggattccga agagtatcat 1620
ctactatatc agaaaactgg agaatcatcg aggtgttatt ccatacaagg tccggatggt 1680
cacttgattt ccttttacgc agatccaaaa aggttctttt taccaatttt ttcagatgag 1740
gtgttgcaca acatgataga cacaatgatt tcatggatta ggtcatgccc tgacttaaaa 1800
gattctctta ttgacattga gactgcacta aggacattga tcctactgat gctcaccaac 1860
ccaacaaaga gaaatcaaaa gcaggttcaa aatattaggt atttagtgat ggccatcgtc 1920
tcagactttt catcgacctc attaatggat aagttgaagg aggatctaat cacacctgcc 1980
gagaaagtgg tgtacaggct gcttcggttt ttgattagga caatttttgg tactggtgaa 2040
aaggtgttat tgagtgcaaa attcaagttt atgttgaatg tgtcatacct gtgtcatttg 2100
atcacaaagg agacccctga tagattgaca gatcagataa aatgttttga aaagttcttt 2160
gagcccaaga gtgagtttgg tttctttgtc aaccctaagg aaacaatcac acccgaagag 2220
gaatgtgttt tttatgaaca aatgaagaag ttcaccggta aagatattga ttgtcagcat 2280
tcaacccctg gtgttaattt agagatcttt agcatgatgg tatcttcatt caacaatggc 2340
accttaattc taaaagggga gaaaaggctc aacaatctgg accccatgac caactctgga 2400
tgtgcgacag cattagatct cgcaagcaac aaaagtgtgg ttgtcaataa acatctgaat 2460
ggagaacggc ttttggagta tgattttaac aaattgcttg ttagtgctgt gagccaaatt 2520
acagagggct tcatgaggaa acaaaagtat aagctgagac actcagatta cgaatataag 2580
gtctcaaagc ttgtctctag attagtcatc ggttccagga aaacagaagt agacaaatta 2640
gaagatgatc cggtagatgt gtgtttcgag ggggaggagg agacaagttt tttcaggagt 2700
ttagaagata aggtcagctc cacaataaca cggtataata gaggcactag gcttaatgaa 2760
gggcaagggg agggagaatt caagaacaca aaaggactac accaccttca gattattttg 2820
tcaggtaaaa gagcttatct gaggaaagtc attttatcag aaatttcatt tcatctagta 2880
gaggactttg atccatcctg tctcaccaat gacgacatga ggtttatttg tgaggctgtt 2940
gaaggttcaa cagaactgtc accattgtat tttacatcag ctgtcaaaga acaatgtggt 3000
ctggatgaga tggcaagaaa cctctgtaga aagttcttct cagagggtga ttggttctca 3060
tgtatgaaga tgatcttgtt acagatgaat gcaaatgcgt attcagggaa gtacagacac 3120
atgcagaggc agagcttaaa ttttaaattt gactgggaca aattggaaga agatgtaaga 3180
attagtgaaa gggaaagcaa ttctgaatct ctaagtaagg ccctttcatt gacaaaatgc 3240
atgagtgctg ctctaaagaa tctgtgtttt tactcagaag aatcaccaac atcatacact 3300
tcagttggcc ctgactctgg gagactaaaa tttgcattgt catacaaaga gcaggttggg 3360
ggaaatagag agctttacat tggggatttg aggacaaaaa tgttcacaag attggtagaa 3420
gattactttg aatccttttc tagtttcttt tcaggatctt gtttaaacaa tgacaaagag 3480
tttgaaaatg caatcttgtc aatgactatc aatgtgagag aagggttgtt aaactacagc 3540
atggatcaca gcaaatgggg accaatgatg tgcccattcc tattcttaat gcttctccaa 3600
aatctcaaac tgggtgatga tcagtacgtg cgttctggaa aagatcatgt tagcaccttg 3660
ttgacttggc atatgcataa acttgttgaa gtccctttcc ctgttgtgaa tgcaatgatg 3720
aaatcatatg ttaaatcaaa actcaagctt ctcaaagggt caggaacgac tgttacggag 3780
agaatcttta gagagtattt tgaaatgggg gtggtgccat ctcacatatc tagtctcatt 3840
gacatgggac aggggatcct acacaatgct tctgattttt acggtttaat tagtgaaagg 3900
tttatcaatt attgtattgg tgtcattttt ggagagaggc cagaagccta tacatcaagt 3960
gatgatcaga tcactttatt tgacaagaga ttgagtgact tagttgatag tgacccagaa 4020
gaagtccttg tcttgctgga attccactct cacttaagtg gtttgttgaa caagttcatc 4080
agtccaaaaa gtgtggttgg gcggtttgca gcggaattca aatccagatt ttatgtgtgg 4140
ggggaggagg tccctctcct cacgaaattt gtgtctgcgg cactacacaa tgttaagtgt 4200
aaagaaccgc atcaactttg tgagacaata gatacgattg ctgatcaagc tatagcaaat 4260
ggagttccag tttttttagt aaactgtatc cagaggagga cactggatct cttgaaatat 4320
gctaatttcc ctttagatcc attcttgtta aacactcaca ctgatgtaaa ggattggtta 4380
gatggttcta gaggttatag aatccaaaga ctcattgaag aattgtgtcc cagtgaaaca 4440
aagatcatga gaaaacttgt aagaagacta catcacaaac tcaagaacgg tgaatgtaac 4500
gaggaatttt ttctagacct cttcaacagg gaaaagaaag aggccatcct tcaattggga 4560
gagattcttg gtcttgagga tgatcttaat gagttggcaa gcatcaattg gttgaatctg 4620
aatgaaatgt tcccattgag gatggttctg agacaaaaag tggtttaccc atcagtaatg 4680
acctttcaag aggaaaagat cccctcattg attaaaacac tccaaaataa gctttgtagt 4740
aagttcacaa gaggtgcaca gaagctgttg tcagaggcaa tcaacaaatc agcttttcag 4800
agttgtgtct catccggctt tataggtctc tgtaagactt taggaagtag gtgtgtgaga 4860
aataaaaaca gggaaaatat gtatatcaga aaggtgcttg aagatctgac catggatgaa 4920
catgtcacaa gggttcacaa acaagatggt gtgatgttgt acatttgcga caagcagaga 4980
cacccagagg ctcaccgtga ccacatcaac cttttgaggc cccttctctg ggactacatt 5040
tgcatctcat tgagcaactc ttttgagctg ggtgtttggg ttttagcaga acctgtgaaa 5100
ggaaagaacg agagtaattc ggctgttagg cacttaaatc catgtgatta tgtagcaaga 5160
aaacctgaga gttcgagact actagaggat aaagtgagtt tgaatcatgt aattcaatct 5220
gtgaggcgac tgtaccccaa aatctttgag gatcagttgc tcccattcat gtctgatgtg 5280
agctcaaaaa atatgagatg gagtcccagg attaaattcc ttgacctttg tgtgctgatt 5340
gacatcaact cagagtcttt gtcactcatt tctcatgttg tcaaatggaa gagggacgaa 5400
cattacactg tgctgttttc tgatctcgtc aactctcacc aacggtcaga ctcaagttta 5460
gttgatgaat ttgttgtcag cacaagggat gtctgcaaga actttttgaa gcaagtgtat 5520
ttcgaatcat ttgtacgaga gtttgttgca acagctagga ccttaggtaa cttttcatgg 5580
ttcccccata aggacatgat gccatctgaa gatggcgctg aagcactggg acccttccaa 5640
tcatttattt tgaaagtggt gaacaagaaa atagagaggc ccatgtttag gaatgacttg 5700
cagtttggtt ttggttggtt ctcttatcgt gtgggggatg ttgtgtgtaa tgccgctatg 5760
ttaattaagc agggtttgac agatccaaaa gcatttaaat ctttaagaga tttgtgggat 5820
tacatgctca gcagcacaga ggggatattg gagttctcaa tcacagtgga tttcacacac 5880
aaccagaaca acactgactg cttgaggaaa ttttcattga tctttgtggt taaatgccaa 5940
ttacagagtc caggtgtagc tgattactta tcgtgctctc attccttcaa aggtgaggtt 6000
gacaggagat tattagatga gtgtctcaat ctgttgagga cagaccccat ctttaaagcg 6060
aatgatggag tctttgacat taggtctgaa gagtttgaag attacatgga agaccctttg 6120
acacttggtg attcactaga acttgaacta ataggttcta gaaggattct gaatgagatc 6180
aaatctactg actttgagag gatagggcct gagtgggaac ctgtgcctct gaccataagg 6240
aagggtgccc tctttgaggg gaggaacttt gttcagaata tctctgtgaa attggagaca 6300
aaggacatga gggtctttct ggcagagctc gagggctgtg gaaaaattgg tgatgtcctc 6360
ggcagcctcc tcctgcaccg attcagaact ggtgagcact tgatggagtc agaaataagt 6420
acagttcttc aggagctctg catggacaga tccgtcatgc tgacaccatt atcttttgtg 6480
ccagattggt tcaccttcag agattgtagg ctctgcttca gcaggtcaaa gaacactgta 6540
atgtatgaga caactggggg caggttcaga ctcaagggga aatcctgtga cgattggctg 6600
gcggagcggg tggccgagga gatcgactag 6630
<210> 56
<211> 2209
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-1.3)
<400> 56
Met Asp Glu Thr Ile Ala Asp Leu Arg Glu Leu Cys Leu Asn Tyr Ile
1 5 10 15
Glu Gln Asp Glu Arg Leu Ser Arg Gln Lys Leu Asn Phe Leu Gly Gln
20 25 30
Arg Glu Pro Arg Met Val Leu Ile Glu Gly Leu Lys Leu Leu Ser Arg
35 40 45
Cys Ile Glu Ile Asp Ser Ala Asp Lys Ser Gly Cys Ile His Asn His
50 55 60
Asp Asp Lys Ser Val Glu Thr Ile Leu Ile Asp Ser Gly Ile Val Cys
65 70 75 80
Pro Gly Leu Pro Leu Ile Ile Pro Asp Gly Tyr Lys Leu Ile Asp Asn
85 90 95
Ser Leu Ile Leu Leu Glu Cys Phe Val Arg Ser Thr Pro Ala Ser Phe
100 105 110
Glu Lys Lys Phe Ile Glu Asp Thr Asn Lys Leu Ala Cys Ile Lys Glu
115 120 125
Asp Leu Ala Val Ala Gly Ile Thr Leu Val Pro Ile Val Asp Gly Arg
130 135 140
Cys Asp Tyr Asp Asn Ser Phe Met Pro Glu Trp Val Asn Phe Lys Phe
145 150 155 160
Arg Asp Leu Leu Phe Lys Leu Leu Glu Tyr Ser Ser Gln Asp Glu Lys
165 170 175
Val Phe Glu Glu Ser Glu Tyr Phe Arg Leu Cys Glu Ser Leu Lys Thr
180 185 190
Thr Val Asp Lys Arg Ser Gly Met Asp Ser Met Lys Ile Leu Lys Asp
195 200 205
Ala Arg Ser Phe His Asn Asp Glu Ile Met Lys Met Cys His Asp Gly
210 215 220
Val Asn Pro Asn Met Ser Cys Asp Asp Val Val Phe Gly Ile Asn Ser
225 230 235 240
Phe Phe Gly Arg Phe Arg Arg Asp Leu Leu Asn Gly Lys Leu Lys Arg
245 250 255
Asn Phe Gln Lys Val Ser Pro Gly Gly Leu Ile Lys Glu Phe Ser Glu
260 265 270
Leu Tyr Glu Thr Leu Thr Asp Asn Asp Asp Ile Leu Met Leu Ser Lys
275 280 285
Glu Ala Val Glu Ser Cys Pro Leu Met Arg Phe Ile Thr Ala Glu Thr
290 295 300
His Gly His Glu Arg Gly Ser Asp Ala Asn Thr Glu Tyr Glu Arg Leu
305 310 315 320
Leu Ser Met Leu Asn Lys Val Lys Ser Leu Lys Leu Leu Asn Thr Arg
325 330 335
Arg Arg Gln Leu Leu Asn Leu Asp Val Leu Cys Leu Ser Ser Leu Ile
340 345 350
Lys Gln Ser Ile Ser Lys Gly Leu Glu Asn Asp Lys His Trp Val Gly
355 360 365
Cys Cys Tyr Ser Ser Val Asn Asp Arg Leu Val Ser Leu Gln Ser Thr
370 375 380
Lys Glu Glu Phe Met Arg Leu Leu Lys Asn Arg Arg Lys Ser Arg Val
385 390 395 400
His Lys Lys Ala Ser Leu Asp Glu Leu Phe Arg Val Ser Ile Asn Glu
405 410 415
Phe Ile Ala Lys Ile Gln Lys Cys Leu Ser Thr Val Gly Leu Ser Phe
420 425 430
Glu His Tyr Gly Leu Ser Glu Cys Leu Val Gln Glu Cys His Ile Pro
435 440 445
Phe Ala Glu Phe Glu Asn Phe Met Arg Ala Gly Thr His Pro Val Met
450 455 460
His Tyr Thr Lys Phe Glu Asp Tyr Thr Phe Gln Pro Asn Ile Glu Gln
465 470 475 480
Leu Arg Gly Leu Gln Ser Leu Arg Lys Leu Ser Ser Val Cys Leu Ala
485 490 495
Leu Thr Asn Ser Met Lys Thr Ser Ser Val Ala Arg Leu Arg Gln Asn
500 505 510
Gln Leu Gly Ser Val Arg Tyr Gln Val Val Glu Cys Lys Glu Val Phe
515 520 525
Cys Gln Ile Ile Lys Leu Asp Ser Glu Glu Tyr His Leu Leu Tyr Gln
530 535 540
Lys Thr Gly Glu Ser Ser Arg Cys Tyr Ser Ile Gln Gly Pro Asp Gly
545 550 555 560
His Leu Ile Ser Phe Tyr Ala Asp Pro Lys Arg Phe Phe Leu Pro Ile
565 570 575
Phe Ser Asp Glu Val Leu His Asn Met Ile Asp Thr Met Ile Ser Trp
580 585 590
Ile Arg Ser Cys Pro Asp Leu Lys Asp Ser Leu Ile Asp Ile Glu Thr
595 600 605
Ala Leu Arg Thr Leu Ile Leu Leu Met Leu Thr Asn Pro Thr Lys Arg
610 615 620
Asn Gln Lys Gln Val Gln Asn Ile Arg Tyr Leu Val Met Ala Ile Val
625 630 635 640
Ser Asp Phe Ser Ser Thr Ser Leu Met Asp Lys Leu Lys Glu Asp Leu
645 650 655
Ile Thr Pro Ala Glu Lys Val Val Tyr Arg Leu Leu Arg Phe Leu Ile
660 665 670
Arg Thr Ile Phe Gly Thr Gly Glu Lys Val Leu Leu Ser Ala Lys Phe
675 680 685
Lys Phe Met Leu Asn Val Ser Tyr Leu Cys His Leu Ile Thr Lys Glu
690 695 700
Thr Pro Asp Arg Leu Thr Asp Gln Ile Lys Cys Phe Glu Lys Phe Phe
705 710 715 720
Glu Pro Lys Ser Glu Phe Gly Phe Phe Val Asn Pro Lys Glu Thr Ile
725 730 735
Thr Pro Glu Glu Glu Cys Val Phe Tyr Glu Gln Met Lys Lys Phe Thr
740 745 750
Gly Lys Asp Ile Asp Cys Gln His Ser Thr Pro Gly Val Asn Leu Glu
755 760 765
Ile Phe Ser Met Met Val Ser Ser Phe Asn Asn Gly Thr Leu Ile Leu
770 775 780
Lys Gly Glu Lys Arg Leu Asn Asn Leu Asp Pro Met Thr Asn Ser Gly
785 790 795 800
Cys Ala Thr Ala Leu Asp Leu Ala Ser Asn Lys Ser Val Val Val Asn
805 810 815
Lys His Leu Asn Gly Glu Arg Leu Leu Glu Tyr Asp Phe Asn Lys Leu
820 825 830
Leu Val Ser Ala Val Ser Gln Ile Thr Glu Gly Phe Met Arg Lys Gln
835 840 845
Lys Tyr Lys Leu Arg His Ser Asp Tyr Glu Tyr Lys Val Ser Lys Leu
850 855 860
Val Ser Arg Leu Val Ile Gly Ser Arg Lys Thr Glu Val Asp Lys Leu
865 870 875 880
Glu Asp Asp Pro Val Asp Val Cys Phe Glu Gly Glu Glu Glu Thr Ser
885 890 895
Phe Phe Arg Ser Leu Glu Asp Lys Val Ser Ser Thr Ile Thr Arg Tyr
900 905 910
Asn Arg Gly Thr Arg Leu Asn Glu Gly Gln Gly Glu Gly Glu Phe Lys
915 920 925
Asn Thr Lys Gly Leu His His Leu Gln Ile Ile Leu Ser Gly Lys Arg
930 935 940
Ala Tyr Leu Arg Lys Val Ile Leu Ser Glu Ile Ser Phe His Leu Val
945 950 955 960
Glu Asp Phe Asp Pro Ser Cys Leu Thr Asn Asp Asp Met Arg Phe Ile
965 970 975
Cys Glu Ala Val Glu Gly Ser Thr Glu Leu Ser Pro Leu Tyr Phe Thr
980 985 990
Ser Ala Val Lys Glu Gln Cys Gly Leu Asp Glu Met Ala Arg Asn Leu
995 1000 1005
Cys Arg Lys Phe Phe Ser Glu Gly Asp Trp Phe Ser Cys Met Lys
1010 1015 1020
Met Ile Leu Leu Gln Met Asn Ala Asn Ala Tyr Ser Gly Lys Tyr
1025 1030 1035
Arg His Met Gln Arg Gln Ser Leu Asn Phe Lys Phe Asp Trp Asp
1040 1045 1050
Lys Leu Glu Glu Asp Val Arg Ile Ser Glu Arg Glu Ser Asn Ser
1055 1060 1065
Glu Ser Leu Ser Lys Ala Leu Ser Leu Thr Lys Cys Met Ser Ala
1070 1075 1080
Ala Leu Lys Asn Leu Cys Phe Tyr Ser Glu Glu Ser Pro Thr Ser
1085 1090 1095
Tyr Thr Ser Val Gly Pro Asp Ser Gly Arg Leu Lys Phe Ala Leu
1100 1105 1110
Ser Tyr Lys Glu Gln Val Gly Gly Asn Arg Glu Leu Tyr Ile Gly
1115 1120 1125
Asp Leu Arg Thr Lys Met Phe Thr Arg Leu Val Glu Asp Tyr Phe
1130 1135 1140
Glu Ser Phe Ser Ser Phe Phe Ser Gly Ser Cys Leu Asn Asn Asp
1145 1150 1155
Lys Glu Phe Glu Asn Ala Ile Leu Ser Met Thr Ile Asn Val Arg
1160 1165 1170
Glu Gly Leu Leu Asn Tyr Ser Met Asp His Ser Lys Trp Gly Pro
1175 1180 1185
Met Met Cys Pro Phe Leu Phe Leu Met Leu Leu Gln Asn Leu Lys
1190 1195 1200
Leu Gly Asp Asp Gln Tyr Val Arg Ser Gly Lys Asp His Val Ser
1205 1210 1215
Thr Leu Leu Thr Trp His Met His Lys Leu Val Glu Val Pro Phe
1220 1225 1230
Pro Val Val Asn Ala Met Met Lys Ser Tyr Val Lys Ser Lys Leu
1235 1240 1245
Lys Leu Leu Lys Gly Ser Gly Thr Thr Val Thr Glu Arg Ile Phe
1250 1255 1260
Arg Glu Tyr Phe Glu Met Gly Val Val Pro Ser His Ile Ser Ser
1265 1270 1275
Leu Ile Asp Met Gly Gln Gly Ile Leu His Asn Ala Ser Asp Phe
1280 1285 1290
Tyr Gly Leu Ile Ser Glu Arg Phe Ile Asn Tyr Cys Ile Gly Val
1295 1300 1305
Ile Phe Gly Glu Arg Pro Glu Ala Tyr Thr Ser Ser Asp Asp Gln
1310 1315 1320
Ile Thr Leu Phe Asp Lys Arg Leu Ser Asp Leu Val Asp Ser Asp
1325 1330 1335
Pro Glu Glu Val Leu Val Leu Leu Glu Phe His Ser His Leu Ser
1340 1345 1350
Gly Leu Leu Asn Lys Phe Ile Ser Pro Lys Ser Val Val Gly Arg
1355 1360 1365
Phe Ala Ala Glu Phe Lys Ser Arg Phe Tyr Val Trp Gly Glu Glu
1370 1375 1380
Val Pro Leu Leu Thr Lys Phe Val Ser Ala Ala Leu His Asn Val
1385 1390 1395
Lys Cys Lys Glu Pro His Gln Leu Cys Glu Thr Ile Asp Thr Ile
1400 1405 1410
Ala Asp Gln Ala Ile Ala Asn Gly Val Pro Val Phe Leu Val Asn
1415 1420 1425
Cys Ile Gln Arg Arg Thr Leu Asp Leu Leu Lys Tyr Ala Asn Phe
1430 1435 1440
Pro Leu Asp Pro Phe Leu Leu Asn Thr His Thr Asp Val Lys Asp
1445 1450 1455
Trp Leu Asp Gly Ser Arg Gly Tyr Arg Ile Gln Arg Leu Ile Glu
1460 1465 1470
Glu Leu Cys Pro Ser Glu Thr Lys Ile Met Arg Lys Leu Val Arg
1475 1480 1485
Arg Leu His His Lys Leu Lys Asn Gly Glu Cys Asn Glu Glu Phe
1490 1495 1500
Phe Leu Asp Leu Phe Asn Arg Glu Lys Lys Glu Ala Ile Leu Gln
1505 1510 1515
Leu Gly Glu Ile Leu Gly Leu Glu Asp Asp Leu Asn Glu Leu Ala
1520 1525 1530
Ser Ile Asn Trp Leu Asn Leu Asn Glu Met Phe Pro Leu Arg Met
1535 1540 1545
Val Leu Arg Gln Lys Val Val Tyr Pro Ser Val Met Thr Phe Gln
1550 1555 1560
Glu Glu Lys Ile Pro Ser Leu Ile Lys Thr Leu Gln Asn Lys Leu
1565 1570 1575
Cys Ser Lys Phe Thr Arg Gly Ala Gln Lys Leu Leu Ser Glu Ala
1580 1585 1590
Ile Asn Lys Ser Ala Phe Gln Ser Cys Val Ser Ser Gly Phe Ile
1595 1600 1605
Gly Leu Cys Lys Thr Leu Gly Ser Arg Cys Val Arg Asn Lys Asn
1610 1615 1620
Arg Glu Asn Met Tyr Ile Arg Lys Val Leu Glu Asp Leu Thr Met
1625 1630 1635
Asp Glu His Val Thr Arg Val His Lys Gln Asp Gly Val Met Leu
1640 1645 1650
Tyr Ile Cys Asp Lys Gln Arg His Pro Glu Ala His Arg Asp His
1655 1660 1665
Ile Asn Leu Leu Arg Pro Leu Leu Trp Asp Tyr Ile Cys Ile Ser
1670 1675 1680
Leu Ser Asn Ser Phe Glu Leu Gly Val Trp Val Leu Ala Glu Pro
1685 1690 1695
Val Lys Gly Lys Asn Glu Ser Asn Ser Ala Val Arg His Leu Asn
1700 1705 1710
Pro Cys Asp Tyr Val Ala Arg Lys Pro Glu Ser Ser Arg Leu Leu
1715 1720 1725
Glu Asp Lys Val Ser Leu Asn His Val Ile Gln Ser Val Arg Arg
1730 1735 1740
Leu Tyr Pro Lys Ile Phe Glu Asp Gln Leu Leu Pro Phe Met Ser
1745 1750 1755
Asp Val Ser Ser Lys Asn Met Arg Trp Ser Pro Arg Ile Lys Phe
1760 1765 1770
Leu Asp Leu Cys Val Leu Ile Asp Ile Asn Ser Glu Ser Leu Ser
1775 1780 1785
Leu Ile Ser His Val Val Lys Trp Lys Arg Asp Glu His Tyr Thr
1790 1795 1800
Val Leu Phe Ser Asp Leu Val Asn Ser His Gln Arg Ser Asp Ser
1805 1810 1815
Ser Leu Val Asp Glu Phe Val Val Ser Thr Arg Asp Val Cys Lys
1820 1825 1830
Asn Phe Leu Lys Gln Val Tyr Phe Glu Ser Phe Val Arg Glu Phe
1835 1840 1845
Val Ala Thr Ala Arg Thr Leu Gly Asn Phe Ser Trp Phe Pro His
1850 1855 1860
Lys Asp Met Met Pro Ser Glu Asp Gly Ala Glu Ala Leu Gly Pro
1865 1870 1875
Phe Gln Ser Phe Ile Leu Lys Val Val Asn Lys Lys Ile Glu Arg
1880 1885 1890
Pro Met Phe Arg Asn Asp Leu Gln Phe Gly Phe Gly Trp Phe Ser
1895 1900 1905
Tyr Arg Val Gly Asp Val Val Cys Asn Ala Ala Met Leu Ile Lys
1910 1915 1920
Gln Gly Leu Thr Asp Pro Lys Ala Phe Lys Ser Leu Arg Asp Leu
1925 1930 1935
Trp Asp Tyr Met Leu Ser Ser Thr Glu Gly Ile Leu Glu Phe Ser
1940 1945 1950
Ile Thr Val Asp Phe Thr His Asn Gln Asn Asn Thr Asp Cys Leu
1955 1960 1965
Arg Lys Phe Ser Leu Ile Phe Val Val Lys Cys Gln Leu Gln Ser
1970 1975 1980
Pro Gly Val Ala Asp Tyr Leu Ser Cys Ser His Ser Phe Lys Gly
1985 1990 1995
Glu Val Asp Arg Arg Leu Leu Asp Glu Cys Leu Asn Leu Leu Arg
2000 2005 2010
Thr Asp Pro Ile Phe Lys Ala Asn Asp Gly Val Phe Asp Ile Arg
2015 2020 2025
Ser Glu Glu Phe Glu Asp Tyr Met Glu Asp Pro Leu Thr Leu Gly
2030 2035 2040
Asp Ser Leu Glu Leu Glu Leu Ile Gly Ser Arg Arg Ile Leu Asn
2045 2050 2055
Glu Ile Lys Ser Thr Asp Phe Glu Arg Ile Gly Pro Glu Trp Glu
2060 2065 2070
Pro Val Pro Leu Thr Ile Arg Lys Gly Ala Leu Phe Glu Gly Arg
2075 2080 2085
Asn Phe Val Gln Asn Ile Ser Val Lys Leu Glu Thr Lys Asp Met
2090 2095 2100
Arg Val Phe Leu Ala Glu Leu Glu Gly Cys Gly Lys Ile Gly Asp
2105 2110 2115
Val Leu Gly Ser Leu Leu Leu His Arg Phe Arg Thr Gly Glu His
2120 2125 2130
Leu Met Glu Ser Glu Ile Ser Thr Val Leu Gln Glu Leu Cys Met
2135 2140 2145
Asp Arg Ser Val Met Leu Thr Pro Leu Ser Phe Val Pro Asp Trp
2150 2155 2160
Phe Thr Phe Arg Asp Cys Arg Leu Cys Phe Ser Arg Ser Lys Asn
2165 2170 2175
Thr Val Met Tyr Glu Thr Thr Gly Gly Arg Phe Arg Leu Lys Gly
2180 2185 2190
Lys Ser Cys Asp Asp Trp Leu Ala Glu Arg Val Ala Glu Glu Ile
2195 2200 2205
Asp
<210> 57
<211> 1497
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-2.1)
<400> 57
atgggtcaga ttgtgacaat gtttgaggct ttgcctcaca tcattgatga ggtcatcaac 60
attgttatta ttgtgctcat tataatcacg agcatcaaag ctgtgtacaa tttcgccacc 120
tgtgggatat tagcactggt cagcttcctt tttttggctg gtaggtcctg tggcatgtac 180
ggccttaatg gtcccgacat ctataaaggg gtttaccagt tcaaatcagt ggagtttgat 240
atgtctcact taaatctgac gatgcccaat gcgtgctcag ccaacaactc tcatcactac 300
atcagtatgg gaagctctgg actggagcta actttcacta acgactccat ccttaatcac 360
aatttttgca acttaacctc cgctttcaac aaaaagactt ttgaccatac actcatgagt 420
atagtctcga gtctgcacct cagtattaga gggaattcca accacaaagc agtgtcttgt 480
gattttaaca atggcatcac cattcaatac aacttgtcat tttcggaccc acagagcgct 540
atgagccagt gtaggacttt cagaggtaga gtcttggaca tgtttagaac tgcctttgga 600
ggaaaataca tgagaagtgg ctggggctgg gcaggttcag atggcaagac cacttggtgc 660
agccaaacaa gctatcagta cctaatcata caaaacagga cttgggaaaa ccactgtaga 720
tatgcaggcc cttttgggat gtctagaatc ctctttgctc aggaaaagac aaagtttctc 780
actaggagac ttgcaggcac attcacctgg accctgtcag actcctcagg agtagaaaat 840
ccaggtggtt attgcctgac caaatggatg atccttgctg cagagctcaa atgttttggg 900
aatacagctg ttgcaaaatg taatgtcaat catgatgaag agttctgtga catgctacga 960
ctaattgatt acaacaaggc cgccctgagt aagttcaagc aagatgtaga gtctgccttg 1020
catgtattca aaacaacagt aaattctctg atttccgatc agctgttgat gaggaatcat 1080
ctaagagatc taatgggggt accatactgt aattactcaa agttctggta tctggaacat 1140
gctaagactg gtgagactag tgtacccaag tgctggcttg tcactaatgg ctcctacttg 1200
aatgagaccc actttagtga tcaaatcgaa caagaagcag ataacatgat cacagagatg 1260
ttgaggaagg actacataaa aagacaaggg agtactcctt tagccttaat ggatcttttg 1320
atgttttcaa catcagcata tctaatcagc atctttctgc atcttgtgaa gataccaaca 1380
catagacaca taaagggcgg ttcatgtcca aagccacacc gcttgaccaa caaggggatc 1440
tgtagttgtg gtgcattcaa ggtgcctggt gtaaaaacta tctggaaaag acgctga 1497
<210> 58
<211> 498
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-2.1)
<400> 58
Met Gly Gln Ile Val Thr Met Phe Glu Ala Leu Pro His Ile Ile Asp
1 5 10 15
Glu Val Ile Asn Ile Val Ile Ile Val Leu Ile Ile Ile Thr Ser Ile
20 25 30
Lys Ala Val Tyr Asn Phe Ala Thr Cys Gly Ile Leu Ala Leu Val Ser
35 40 45
Phe Leu Phe Leu Ala Gly Arg Ser Cys Gly Met Tyr Gly Leu Asn Gly
50 55 60
Pro Asp Ile Tyr Lys Gly Val Tyr Gln Phe Lys Ser Val Glu Phe Asp
65 70 75 80
Met Ser His Leu Asn Leu Thr Met Pro Asn Ala Cys Ser Ala Asn Asn
85 90 95
Ser His His Tyr Ile Ser Met Gly Ser Ser Gly Leu Glu Leu Thr Phe
100 105 110
Thr Asn Asp Ser Ile Leu Asn His Asn Phe Cys Asn Leu Thr Ser Ala
115 120 125
Phe Asn Lys Lys Thr Phe Asp His Thr Leu Met Ser Ile Val Ser Ser
130 135 140
Leu His Leu Ser Ile Arg Gly Asn Ser Asn His Lys Ala Val Ser Cys
145 150 155 160
Asp Phe Asn Asn Gly Ile Thr Ile Gln Tyr Asn Leu Ser Phe Ser Asp
165 170 175
Pro Gln Ser Ala Met Ser Gln Cys Arg Thr Phe Arg Gly Arg Val Leu
180 185 190
Asp Met Phe Arg Thr Ala Phe Gly Gly Lys Tyr Met Arg Ser Gly Trp
195 200 205
Gly Trp Ala Gly Ser Asp Gly Lys Thr Thr Trp Cys Ser Gln Thr Ser
210 215 220
Tyr Gln Tyr Leu Ile Ile Gln Asn Arg Thr Trp Glu Asn His Cys Arg
225 230 235 240
Tyr Ala Gly Pro Phe Gly Met Ser Arg Ile Leu Phe Ala Gln Glu Lys
245 250 255
Thr Lys Phe Leu Thr Arg Arg Leu Ala Gly Thr Phe Thr Trp Thr Leu
260 265 270
Ser Asp Ser Ser Gly Val Glu Asn Pro Gly Gly Tyr Cys Leu Thr Lys
275 280 285
Trp Met Ile Leu Ala Ala Glu Leu Lys Cys Phe Gly Asn Thr Ala Val
290 295 300
Ala Lys Cys Asn Val Asn His Asp Glu Glu Phe Cys Asp Met Leu Arg
305 310 315 320
Leu Ile Asp Tyr Asn Lys Ala Ala Leu Ser Lys Phe Lys Gln Asp Val
325 330 335
Glu Ser Ala Leu His Val Phe Lys Thr Thr Val Asn Ser Leu Ile Ser
340 345 350
Asp Gln Leu Leu Met Arg Asn His Leu Arg Asp Leu Met Gly Val Pro
355 360 365
Tyr Cys Asn Tyr Ser Lys Phe Trp Tyr Leu Glu His Ala Lys Thr Gly
370 375 380
Glu Thr Ser Val Pro Lys Cys Trp Leu Val Thr Asn Gly Ser Tyr Leu
385 390 395 400
Asn Glu Thr His Phe Ser Asp Gln Ile Glu Gln Glu Ala Asp Asn Met
405 410 415
Ile Thr Glu Met Leu Arg Lys Asp Tyr Ile Lys Arg Gln Gly Ser Thr
420 425 430
Pro Leu Ala Leu Met Asp Leu Leu Met Phe Ser Thr Ser Ala Tyr Leu
435 440 445
Ile Ser Ile Phe Leu His Leu Val Lys Ile Pro Thr His Arg His Ile
450 455 460
Lys Gly Gly Ser Cys Pro Lys Pro His Arg Leu Thr Asn Lys Gly Ile
465 470 475 480
Cys Ser Cys Gly Ala Phe Lys Val Pro Gly Val Lys Thr Ile Trp Lys
485 490 495
Arg Arg
<210> 59
<211> 1677
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-2.1)
<400> 59
atgtctttgt ccaaagaagt caaaagcttt cagtggacac aggcgttgag gagggagttg 60
cagagtttta catcagatgt aaaggctgcc gtcatcaagg acgcaaccag tcttctaaat 120
gggttggact tttctgaagt cagcaacgtt cagaggatca tgagaaagga aaggagggat 180
gataaagact tgcagagact caggagtctt aaccagactg tgcattctct tgttgatctg 240
aagtctacat caaagaaaaa tgttctgaaa gtgggaagac ttagtgcaga ggaattgatg 300
acccttgcag ctgatcttga gaagctgaag gccaaaatta tgagaactga gaggcctcaa 360
gcttctggag tctacatggg aaatttgaca gcacaacaac ttgatcaaag atcccaaata 420
ctgcaaatgg ttgggatgag aagacctcag cagggtgcaa gtggtgtagt aagggtttgg 480
gatgtgaagg actcatcact tctgaacaat cagttcggca caatgccaag cctgacaatg 540
gcttgcatgg caaaacagtc acagacccca ctcaatgatg ttgtgcaggc actcacagac 600
cttggcttac tttacacagt caaatacccg aatctcagtg atcttgaaag gctaaaggat 660
aaacacccag ttctgggggt cattactgaa cagcaatcta gtatcaatat ctctggttat 720
aatttcagtc ttggtgcagc tgtgaaagcg ggggcagctc tgctagatgg agggaacatg 780
ctggaatcta tcttgatcaa accgagcaac agtgaggatc tcctaaaagc agtcctcggg 840
gccaaaaaga aactcaacat gtttgtctca gatcaagttg gagatagaaa tccctatgaa 900
aacatccttt ataaagtctg tctttcaggt gaaggatggc catacatagc ctgtagaacg 960
tcagttgtgg ggagagcatg ggagaacaca acaattgatc tcacaaatga aaaacttgtt 1020
gccaactcat ctaggccagt gcctggagca gcaggcccac ctcaggtggg cttgagttac 1080
agtcagacaa tgctgttgaa agacttgatg ggagggattg atcccaatgc tcccacatgg 1140
attgacattg agggcaggtt caatgatcca gtggagatag caatattcca accacaaaat 1200
gggcaattca tacattttta cagggaacct acggaccaga agcaattcaa gcaggactca 1260
aagtattcac acggcatgga tcttgctgat ctcttcaatg cacagcctgg gctgacctca 1320
tcagttatag gtgctctccc acaagggatg gttttgagct gtcaaggttc tgatgacatc 1380
agaaagcttc tggactcaca aaatagaagg gacataaaac tcattgatgt tgagatgacc 1440
aaggaggcct caagagaata tgaagataaa gtgtgggaca aatatggctg gctatgcaaa 1500
atgcacactg gggtagtgag agacaaaaag aagaaagaga tcaccccaca ctgtgcactc 1560
atggactgca tcatttttga gagtgcttcc aaggcaagac tccctgatct aaaaaccgtt 1620
cacaacatcc tgccacatga tttaatcttc agaggaccca atgttgtgac actctaa 1677
<210> 60
<211> 558
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-2.1)
<400> 60
Met Ser Leu Ser Lys Glu Val Lys Ser Phe Gln Trp Thr Gln Ala Leu
1 5 10 15
Arg Arg Glu Leu Gln Ser Phe Thr Ser Asp Val Lys Ala Ala Val Ile
20 25 30
Lys Asp Ala Thr Ser Leu Leu Asn Gly Leu Asp Phe Ser Glu Val Ser
35 40 45
Asn Val Gln Arg Ile Met Arg Lys Glu Arg Arg Asp Asp Lys Asp Leu
50 55 60
Gln Arg Leu Arg Ser Leu Asn Gln Thr Val His Ser Leu Val Asp Leu
65 70 75 80
Lys Ser Thr Ser Lys Lys Asn Val Leu Lys Val Gly Arg Leu Ser Ala
85 90 95
Glu Glu Leu Met Thr Leu Ala Ala Asp Leu Glu Lys Leu Lys Ala Lys
100 105 110
Ile Met Arg Thr Glu Arg Pro Gln Ala Ser Gly Val Tyr Met Gly Asn
115 120 125
Leu Thr Ala Gln Gln Leu Asp Gln Arg Ser Gln Ile Leu Gln Met Val
130 135 140
Gly Met Arg Arg Pro Gln Gln Gly Ala Ser Gly Val Val Arg Val Trp
145 150 155 160
Asp Val Lys Asp Ser Ser Leu Leu Asn Asn Gln Phe Gly Thr Met Pro
165 170 175
Ser Leu Thr Met Ala Cys Met Ala Lys Gln Ser Gln Thr Pro Leu Asn
180 185 190
Asp Val Val Gln Ala Leu Thr Asp Leu Gly Leu Leu Tyr Thr Val Lys
195 200 205
Tyr Pro Asn Leu Ser Asp Leu Glu Arg Leu Lys Asp Lys His Pro Val
210 215 220
Leu Gly Val Ile Thr Glu Gln Gln Ser Ser Ile Asn Ile Ser Gly Tyr
225 230 235 240
Asn Phe Ser Leu Gly Ala Ala Val Lys Ala Gly Ala Ala Leu Leu Asp
245 250 255
Gly Gly Asn Met Leu Glu Ser Ile Leu Ile Lys Pro Ser Asn Ser Glu
260 265 270
Asp Leu Leu Lys Ala Val Leu Gly Ala Lys Lys Lys Leu Asn Met Phe
275 280 285
Val Ser Asp Gln Val Gly Asp Arg Asn Pro Tyr Glu Asn Ile Leu Tyr
290 295 300
Lys Val Cys Leu Ser Gly Glu Gly Trp Pro Tyr Ile Ala Cys Arg Thr
305 310 315 320
Ser Val Val Gly Arg Ala Trp Glu Asn Thr Thr Ile Asp Leu Thr Asn
325 330 335
Glu Lys Leu Val Ala Asn Ser Ser Arg Pro Val Pro Gly Ala Ala Gly
340 345 350
Pro Pro Gln Val Gly Leu Ser Tyr Ser Gln Thr Met Leu Leu Lys Asp
355 360 365
Leu Met Gly Gly Ile Asp Pro Asn Ala Pro Thr Trp Ile Asp Ile Glu
370 375 380
Gly Arg Phe Asn Asp Pro Val Glu Ile Ala Ile Phe Gln Pro Gln Asn
385 390 395 400
Gly Gln Phe Ile His Phe Tyr Arg Glu Pro Thr Asp Gln Lys Gln Phe
405 410 415
Lys Gln Asp Ser Lys Tyr Ser His Gly Met Asp Leu Ala Asp Leu Phe
420 425 430
Asn Ala Gln Pro Gly Leu Thr Ser Ser Val Ile Gly Ala Leu Pro Gln
435 440 445
Gly Met Val Leu Ser Cys Gln Gly Ser Asp Asp Ile Arg Lys Leu Leu
450 455 460
Asp Ser Gln Asn Arg Arg Asp Ile Lys Leu Ile Asp Val Glu Met Thr
465 470 475 480
Lys Glu Ala Ser Arg Glu Tyr Glu Asp Lys Val Trp Asp Lys Tyr Gly
485 490 495
Trp Leu Cys Lys Met His Thr Gly Val Val Arg Asp Lys Lys Lys Lys
500 505 510
Glu Ile Thr Pro His Cys Ala Leu Met Asp Cys Ile Ile Phe Glu Ser
515 520 525
Ala Ser Lys Ala Arg Leu Pro Asp Leu Lys Thr Val His Asn Ile Leu
530 535 540
Pro His Asp Leu Ile Phe Arg Gly Pro Asn Val Val Thr Leu
545 550 555
<210> 61
<211> 273
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-2.1)
<400> 61
atgggccaag gcaagtccaa agaagaaagg gacaccagca atacaggcag agcagagctt 60
ttgccagaca ccacctatct tggtcctcta aattgtaaat catgttggca gaaatttgac 120
agcttggtta gatgccatga ccactatctt tgcagacact gtctgaatct cctgctgtca 180
gtttccgaca gatgtcctct ctgtaagtat ccactgccaa ccaaactgaa ggtgtcaaca 240
gtcccaagct ccccacctcc ctatgaggag tga 273
<210> 62
<211> 90
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-2.1)
<400> 62
Met Gly Gln Gly Lys Ser Lys Glu Glu Arg Asp Thr Ser Asn Thr Gly
1 5 10 15
Arg Ala Glu Leu Leu Pro Asp Thr Thr Tyr Leu Gly Pro Leu Asn Cys
20 25 30
Lys Ser Cys Trp Gln Lys Phe Asp Ser Leu Val Arg Cys His Asp His
35 40 45
Tyr Leu Cys Arg His Cys Leu Asn Leu Leu Leu Ser Val Ser Asp Arg
50 55 60
Cys Pro Leu Cys Lys Tyr Pro Leu Pro Thr Lys Leu Lys Val Ser Thr
65 70 75 80
Val Pro Ser Ser Pro Pro Pro Tyr Glu Glu
85 90
<210> 63
<211> 6630
<212> DNA
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-2.1)
<400> 63
atggatgaaa ctattgcaga tttgagagag ttgtgtctaa attacataga acaggacgaa 60
aggctgtcaa ggcaaaaact caacttcctg ggacaaagag aacccagaat ggtgctaatt 120
gagggactca aattgttatc acgctgtata gagatagaca gtgcagacaa aagtggttgc 180
atacacaacc acgatgacaa atctgttgaa acaatcctaa tagactctgg gattgtgtgt 240
ccaggactgc cactcatcat ccctgatggt tataagttga ttgacaattc ccttattctt 300
cttgaatgtt ttgttagaag cacaccagct agttttgaaa agaagttcat tgaggacacc 360
aacaaactag catgcatcaa agaagatctt gctgttgcag gcatcacact ggttccaata 420
gtggatggtc gttgtgatta tgataacagt ttcatgccag aatgggtgaa ttttaagttc 480
agagacctcc tatttaaact cctggagtat tctagtcaag atgagaaagt ttttgaggag 540
tctgaatact tcaggctctg tgagtctctt aagaccactg ttgacaaacg ttccggcatg 600
gactcaatga aaattttgaa agacgcaaga tcatttcata acgatgagat tatgaaaatg 660
tgccacgatg gtgtcaaccc caacatgagt tgcgatgatg tggtctttgg cataaattcc 720
ttttttggca ggtttaggag ggacctgtta aatgggaaac tcaaaaggaa tttccaaaag 780
gtcagccctg ggggcttaat caaggaattc tctgaacttt atgaaaccct tactgataat 840
gatgacatat taatgttgag caaagaggca gttgaatcct gccccttaat gaggttcatt 900
acagcagaga cccatgggca tgagagagga agcgatgcta acactgagta tgaaaggcta 960
ctctctatgt tgaacaaggt gaaaagttta aaattattaa acactagaag gagacagctg 1020
ctgaacttag atgtcttatg tctttcttca cttattaagc agtcaatttc caaagggttg 1080
gaaaatgata aacattgggt tggttgttgc tacagtagtg tgaatgatag gcttgtgagc 1140
cttcaaagta ccaaagaaga attcatgaga cttttgaaga acagaagaaa atcaagagtg 1200
cacaaaaagg catctcttga tgagcttttt agggtatcca taaatgagtt catagcaaaa 1260
atccagaaat gcctatcaac agtgggactt agttttgagc attacggact atcagaatgc 1320
ctcgtgcaag aatgccatat accatttgct gaatttgaga actttatgag agccgggact 1380
catcctgtaa tgcattacac aaaatttgaa gattacactt tccagcctaa catagagcaa 1440
ttgaggggtt tacagagttt gagaaaactg tcatctgttt gtttggctct aacaaacagc 1500
atgaaaacaa gctcagttgc aaggttgaga cagaaccaac tggggtctgt gagatatcaa 1560
gtggtggagt gcaaagaggt gttttgccag ataataaaac tggattccga agagtatcat 1620
ctactatatc agaaaactgg agaatcatcg aggtgttatt ccatacaagg tccggatggt 1680
cacttgattt ccttttacgc agatccaaaa aggttctttt taccaatttt ttcagatgag 1740
gtgttgcaca acatgataga cacaatgatt tcatggatta ggtcatgccc tgacttaaaa 1800
gattctctta ttgacattga gactgcacta aggacattga tcctactgat gctcaccaac 1860
ccaacaaaga gaaatcaaaa gcaggttcaa aatattaggt atttagtgat ggccatcgtc 1920
tcagactttt catcgacctc attaatggat aagttgaagg aggatctaat cacacctgcc 1980
gagaaagtgg tgtacaggct gcttcggttt ttgattagga caatttttgg tactggtgaa 2040
aaggtgttat tgagtgcaaa atttaagttt atgttgaatg tgtcatacct gtgtcatttg 2100
atcacaaagg agacccctga tagattgaca gatcagataa aatgttttga aaagttcttt 2160
gagcccaaga gtgagtttgg tttctttgtc aaccctaagg aaacaatcac acccgaagag 2220
gaatgtgttt tttatgaaca aatgaagaag ttcaccggta aagatattga ttgtcagcat 2280
tcaacccctg gtgttaattt agagatcttt agcatgatgg tatcttcatt caacaatggc 2340
accttaattc taaaagggga gaaaaggctc aacaatctgg accccatgac caactctgga 2400
tgtgcgacag cattagatct cgcaagcaac aaaagtgtgg ttgtcaataa acatctgaat 2460
ggagaacggc ttttggagta tgattttaac aaattgcttg ttagtgctgt gagccaaatt 2520
acagagggct tcatgaggaa acaaaagtat aagctgagac actcagatta cgaatataag 2580
gtctcaaagc ttgtctctag attagtcatc ggttccagga aaacagaagt agacaaattg 2640
gaagatgatc cggtagatgt gtgtttcgag ggggaggagg agacaagttt tttcaggagt 2700
ttagaagata aggtcagctc cacaataaca cggtataata gaggcactag gcttaatgaa 2760
gggcaagggg agggagaatt caagaacaca aaaggactac accaccttca gattattttg 2820
tcaggtaaaa gagcttatct gaggaaagtc attttatcag aaatttcatt tcatctagta 2880
gaggactttg atccatcctg tctcaccaat gacgacatga ggtttatttg tgaggctgtt 2940
gaaggttcaa cagaactgtc accattgtat tttacatcag ctgtcaaaga acaatgtggt 3000
ctggatgaga tggcaagaaa cctctgtaga aagttcttct cagagggtga ttggttctca 3060
tgtatgaaga tgatcttgtt acagatgaat gcaaatgcgt attcagggaa gtacagacac 3120
atgcagaggc agagcttaaa ttttaaattt gactgggaca aattggaaga agatgtaaga 3180
attagtgaaa gggaaagcaa ttctgaatct ctaagtaagg ccctttcatt gacaaaatgc 3240
atgagtgctg ctctaaagaa tctgtgtttt tactcagaag aatcaccaac atcatacact 3300
tcagttggcc ctgactctgg gagactaaaa tttgcattgt catacaaaga gcaggttggg 3360
ggaaatagag agctttacat tggggatttg aggacaaaaa tgttcacaag attggtagaa 3420
gattattttg aatccttttc tagtttcttt tcaggatctt gtttaaacaa tgacaaagag 3480
tttgaaaatg caatcttgtc aatgactatc aatgtgagag aagggttgtt aaactacagc 3540
atggatcaca gcaaatgggg accaatgatg tgcccattcc tattcttaat gcttctccaa 3600
aatctcaaac tgggtgatga tcagtacgtg cgttctggaa aagatcatgt tagcaccttg 3660
ttgacttggc atatgcataa acttgttgaa gtccctttcc ctgttgtgaa tgcaatgatg 3720
aaatcatatg ttaaatcaaa actcaagctt ctcaaagggt caggaacgac tgttacggag 3780
agaatcttta gagagtattt tgaaatgggg gtggtgccat ctcacatatc tagtctcatt 3840
gacatgggac aggggatcct acacaatgct tctgattttt acggtttaat tagtgaaagg 3900
tttatcaatt attgtattgg tgtcattttt ggagagaggc cagaagccta tacatcaagt 3960
gatgatcaga tcactttatt tgacaagaga ttgagtgact tagttgatag tgacccagaa 4020
gaagtccttg tcttgctgga attccactct cacttaagtg gtttgttgaa caagttcatc 4080
agtccaaaaa gtgtggttgg gcggtttgca gcggaattca aatccagatt ttatgtgtgg 4140
ggggaggagg tccctctcct cacgaaattt gtgtctgcgg cactacacaa tgttaagtgt 4200
aaagaaccgc atcaactttg tgagacaata gatacgattg ctgatcaagc tatagcaaat 4260
ggagttccag tttttttagt aaactgtatc cagaggagga cactggatct cttgaaatat 4320
gctaatttcc ctttagatcc attcttgtta aacactcaca ctgatgtaaa ggattggtta 4380
gatggttcta gaggttatag aatccaaaga ctcattgaag aattgtgtcc cagtgaaaca 4440
aagatcatga gaaaacttgt aagaagacta catcacaaac tcaagaacgg tgaatgtaac 4500
gaggaatttt ttctagacct cttcaacagg gaaaagaaag aggccatcct tcaattggga 4560
gagattcttg gtcttgagga tgatcttaat gagttggcaa gcatcaattg gttgaatctg 4620
aatgaaatgt tcccattgag gatggttctg agacaaaaag tggtttaccc atcagtaatg 4680
acctttcaag aggaaaagat cccctcattg attaaaacac tccaaaataa gctttgtagt 4740
aagttcacaa gaggtgcaca gaagctgttg tcagaggcaa tcaacaaatc agcttttcag 4800
agttgtgtct catccggctt tataggtctc tgtaagactt taggaagtag gtgtgtgaga 4860
aataaaaaca gggaaaatat gtatatcaga aaggtgcttg aagatctgac catggatgaa 4920
catgtcacaa gggttcacaa acaagatggt gtgatgttgt acatttgcga caagcagaga 4980
cacccagagg ctcaccgtga ccacatcaac cttttgaggc cccttctctg ggactacatt 5040
tgcatctcat tgagcaactc ttttgagctg ggtgtttggg ttttagcaga acctgtgaaa 5100
ggaaagaacg agagtaattc ggctgttagg cacttaaatc catgtgatta tgtagcaaga 5160
aaacctgaga gttcgagact actagaggat aaagtgagtt tgaatcatgt aattcaatct 5220
gtgaggcgac tgtaccccaa aatctttgag gatcagttgc tcccattcat gtctgatgtg 5280
agctcaaaaa atatgagatg gagtcccagg attaaattcc ttgacctttg tgtgctgatt 5340
gacatcaact cagagtcttt gtcactcatt tctcatgttg tcaaatggaa gagggacgaa 5400
cattacactg tgctgttttc tgatctcgtc aactctcacc aacggtcaga ctcaagttta 5460
gttgatgaat ttgttgtcag cacaagggat gtctgcaaga actttttgaa gcaagtgtat 5520
ttcgaatcat ttgtacgaga gtttgttgca acagctagga ccttaggtaa cttttcatgg 5580
ttcccccata aggacatgat gccatctgaa gatggcgctg aagcactggg acccttccaa 5640
tcatttattt tgaaagtggt gaacaagaaa atagagaggc ccatgtttag gaatgacttg 5700
cagtttggtt ttggttggtt ctcttatcgt gtgggggatg ttgtgtgtaa tgccgctatg 5760
ttaattaagc agggtttgac agatccaaaa gcatttaaat ctttaagaga tttgtgggat 5820
tacatgctca gcagcacaga ggggatattg gagttctcaa tcacagtgga tttcacacac 5880
aaccagaaca acactgactg cttgaggaaa ttttcattga tctttgtggt taaatgccaa 5940
ttacagagtc caggtgtagc tgattactta tcgtgctctc atttcttcaa aggtgaggtt 6000
gacaggagat tattagatga gtgtctcaat ctgttgagga cagaccccat ctttaaagcg 6060
aatgatggag tctttgacat taggtctgaa gagtttgaag attacatgga agaccctttg 6120
acacttggtg attcactaga acttgaacta ataggttcta gaaggattct gaatgagatc 6180
aaatctactg actttgagag gatagggcct gagtgggaac ctgtgcctct gaccataagg 6240
aagggtgccc tctttgaggg gaggaacttt gttcagaata tctctgtgaa attggagaca 6300
aaggacatga gggtctttct ggcagagctc gagggctgtg gagaaattgg tgatgtcctc 6360
ggcagcctcc tcctgcaccg attcagaact ggtgagcact tgatggagtc agaaataagt 6420
acagttcttc aggagctctg catggacaga tccgtcatgc tgacaccatt atcttttgtg 6480
ccagattggt tcaccttcag agattgtagg ctctgcttca gcaggtcaaa gaacactgta 6540
atgtatgaga caactggggg caggttcaga ctcaagggga aatcctgtga cgattggctg 6600
gcggagcggg tggccgagga gatcgactag 6630
<210> 64
<211> 2209
<212> PRT
<213> 淋巴细胞性脉络丛脑膜炎病毒(突变体P52-2.1)
<400> 64
Met Asp Glu Thr Ile Ala Asp Leu Arg Glu Leu Cys Leu Asn Tyr Ile
1 5 10 15
Glu Gln Asp Glu Arg Leu Ser Arg Gln Lys Leu Asn Phe Leu Gly Gln
20 25 30
Arg Glu Pro Arg Met Val Leu Ile Glu Gly Leu Lys Leu Leu Ser Arg
35 40 45
Cys Ile Glu Ile Asp Ser Ala Asp Lys Ser Gly Cys Ile His Asn His
50 55 60
Asp Asp Lys Ser Val Glu Thr Ile Leu Ile Asp Ser Gly Ile Val Cys
65 70 75 80
Pro Gly Leu Pro Leu Ile Ile Pro Asp Gly Tyr Lys Leu Ile Asp Asn
85 90 95
Ser Leu Ile Leu Leu Glu Cys Phe Val Arg Ser Thr Pro Ala Ser Phe
100 105 110
Glu Lys Lys Phe Ile Glu Asp Thr Asn Lys Leu Ala Cys Ile Lys Glu
115 120 125
Asp Leu Ala Val Ala Gly Ile Thr Leu Val Pro Ile Val Asp Gly Arg
130 135 140
Cys Asp Tyr Asp Asn Ser Phe Met Pro Glu Trp Val Asn Phe Lys Phe
145 150 155 160
Arg Asp Leu Leu Phe Lys Leu Leu Glu Tyr Ser Ser Gln Asp Glu Lys
165 170 175
Val Phe Glu Glu Ser Glu Tyr Phe Arg Leu Cys Glu Ser Leu Lys Thr
180 185 190
Thr Val Asp Lys Arg Ser Gly Met Asp Ser Met Lys Ile Leu Lys Asp
195 200 205
Ala Arg Ser Phe His Asn Asp Glu Ile Met Lys Met Cys His Asp Gly
210 215 220
Val Asn Pro Asn Met Ser Cys Asp Asp Val Val Phe Gly Ile Asn Ser
225 230 235 240
Phe Phe Gly Arg Phe Arg Arg Asp Leu Leu Asn Gly Lys Leu Lys Arg
245 250 255
Asn Phe Gln Lys Val Ser Pro Gly Gly Leu Ile Lys Glu Phe Ser Glu
260 265 270
Leu Tyr Glu Thr Leu Thr Asp Asn Asp Asp Ile Leu Met Leu Ser Lys
275 280 285
Glu Ala Val Glu Ser Cys Pro Leu Met Arg Phe Ile Thr Ala Glu Thr
290 295 300
His Gly His Glu Arg Gly Ser Asp Ala Asn Thr Glu Tyr Glu Arg Leu
305 310 315 320
Leu Ser Met Leu Asn Lys Val Lys Ser Leu Lys Leu Leu Asn Thr Arg
325 330 335
Arg Arg Gln Leu Leu Asn Leu Asp Val Leu Cys Leu Ser Ser Leu Ile
340 345 350
Lys Gln Ser Ile Ser Lys Gly Leu Glu Asn Asp Lys His Trp Val Gly
355 360 365
Cys Cys Tyr Ser Ser Val Asn Asp Arg Leu Val Ser Leu Gln Ser Thr
370 375 380
Lys Glu Glu Phe Met Arg Leu Leu Lys Asn Arg Arg Lys Ser Arg Val
385 390 395 400
His Lys Lys Ala Ser Leu Asp Glu Leu Phe Arg Val Ser Ile Asn Glu
405 410 415
Phe Ile Ala Lys Ile Gln Lys Cys Leu Ser Thr Val Gly Leu Ser Phe
420 425 430
Glu His Tyr Gly Leu Ser Glu Cys Leu Val Gln Glu Cys His Ile Pro
435 440 445
Phe Ala Glu Phe Glu Asn Phe Met Arg Ala Gly Thr His Pro Val Met
450 455 460
His Tyr Thr Lys Phe Glu Asp Tyr Thr Phe Gln Pro Asn Ile Glu Gln
465 470 475 480
Leu Arg Gly Leu Gln Ser Leu Arg Lys Leu Ser Ser Val Cys Leu Ala
485 490 495
Leu Thr Asn Ser Met Lys Thr Ser Ser Val Ala Arg Leu Arg Gln Asn
500 505 510
Gln Leu Gly Ser Val Arg Tyr Gln Val Val Glu Cys Lys Glu Val Phe
515 520 525
Cys Gln Ile Ile Lys Leu Asp Ser Glu Glu Tyr His Leu Leu Tyr Gln
530 535 540
Lys Thr Gly Glu Ser Ser Arg Cys Tyr Ser Ile Gln Gly Pro Asp Gly
545 550 555 560
His Leu Ile Ser Phe Tyr Ala Asp Pro Lys Arg Phe Phe Leu Pro Ile
565 570 575
Phe Ser Asp Glu Val Leu His Asn Met Ile Asp Thr Met Ile Ser Trp
580 585 590
Ile Arg Ser Cys Pro Asp Leu Lys Asp Ser Leu Ile Asp Ile Glu Thr
595 600 605
Ala Leu Arg Thr Leu Ile Leu Leu Met Leu Thr Asn Pro Thr Lys Arg
610 615 620
Asn Gln Lys Gln Val Gln Asn Ile Arg Tyr Leu Val Met Ala Ile Val
625 630 635 640
Ser Asp Phe Ser Ser Thr Ser Leu Met Asp Lys Leu Lys Glu Asp Leu
645 650 655
Ile Thr Pro Ala Glu Lys Val Val Tyr Arg Leu Leu Arg Phe Leu Ile
660 665 670
Arg Thr Ile Phe Gly Thr Gly Glu Lys Val Leu Leu Ser Ala Lys Phe
675 680 685
Lys Phe Met Leu Asn Val Ser Tyr Leu Cys His Leu Ile Thr Lys Glu
690 695 700
Thr Pro Asp Arg Leu Thr Asp Gln Ile Lys Cys Phe Glu Lys Phe Phe
705 710 715 720
Glu Pro Lys Ser Glu Phe Gly Phe Phe Val Asn Pro Lys Glu Thr Ile
725 730 735
Thr Pro Glu Glu Glu Cys Val Phe Tyr Glu Gln Met Lys Lys Phe Thr
740 745 750
Gly Lys Asp Ile Asp Cys Gln His Ser Thr Pro Gly Val Asn Leu Glu
755 760 765
Ile Phe Ser Met Met Val Ser Ser Phe Asn Asn Gly Thr Leu Ile Leu
770 775 780
Lys Gly Glu Lys Arg Leu Asn Asn Leu Asp Pro Met Thr Asn Ser Gly
785 790 795 800
Cys Ala Thr Ala Leu Asp Leu Ala Ser Asn Lys Ser Val Val Val Asn
805 810 815
Lys His Leu Asn Gly Glu Arg Leu Leu Glu Tyr Asp Phe Asn Lys Leu
820 825 830
Leu Val Ser Ala Val Ser Gln Ile Thr Glu Gly Phe Met Arg Lys Gln
835 840 845
Lys Tyr Lys Leu Arg His Ser Asp Tyr Glu Tyr Lys Val Ser Lys Leu
850 855 860
Val Ser Arg Leu Val Ile Gly Ser Arg Lys Thr Glu Val Asp Lys Leu
865 870 875 880
Glu Asp Asp Pro Val Asp Val Cys Phe Glu Gly Glu Glu Glu Thr Ser
885 890 895
Phe Phe Arg Ser Leu Glu Asp Lys Val Ser Ser Thr Ile Thr Arg Tyr
900 905 910
Asn Arg Gly Thr Arg Leu Asn Glu Gly Gln Gly Glu Gly Glu Phe Lys
915 920 925
Asn Thr Lys Gly Leu His His Leu Gln Ile Ile Leu Ser Gly Lys Arg
930 935 940
Ala Tyr Leu Arg Lys Val Ile Leu Ser Glu Ile Ser Phe His Leu Val
945 950 955 960
Glu Asp Phe Asp Pro Ser Cys Leu Thr Asn Asp Asp Met Arg Phe Ile
965 970 975
Cys Glu Ala Val Glu Gly Ser Thr Glu Leu Ser Pro Leu Tyr Phe Thr
980 985 990
Ser Ala Val Lys Glu Gln Cys Gly Leu Asp Glu Met Ala Arg Asn Leu
995 1000 1005
Cys Arg Lys Phe Phe Ser Glu Gly Asp Trp Phe Ser Cys Met Lys
1010 1015 1020
Met Ile Leu Leu Gln Met Asn Ala Asn Ala Tyr Ser Gly Lys Tyr
1025 1030 1035
Arg His Met Gln Arg Gln Ser Leu Asn Phe Lys Phe Asp Trp Asp
1040 1045 1050
Lys Leu Glu Glu Asp Val Arg Ile Ser Glu Arg Glu Ser Asn Ser
1055 1060 1065
Glu Ser Leu Ser Lys Ala Leu Ser Leu Thr Lys Cys Met Ser Ala
1070 1075 1080
Ala Leu Lys Asn Leu Cys Phe Tyr Ser Glu Glu Ser Pro Thr Ser
1085 1090 1095
Tyr Thr Ser Val Gly Pro Asp Ser Gly Arg Leu Lys Phe Ala Leu
1100 1105 1110
Ser Tyr Lys Glu Gln Val Gly Gly Asn Arg Glu Leu Tyr Ile Gly
1115 1120 1125
Asp Leu Arg Thr Lys Met Phe Thr Arg Leu Val Glu Asp Tyr Phe
1130 1135 1140
Glu Ser Phe Ser Ser Phe Phe Ser Gly Ser Cys Leu Asn Asn Asp
1145 1150 1155
Lys Glu Phe Glu Asn Ala Ile Leu Ser Met Thr Ile Asn Val Arg
1160 1165 1170
Glu Gly Leu Leu Asn Tyr Ser Met Asp His Ser Lys Trp Gly Pro
1175 1180 1185
Met Met Cys Pro Phe Leu Phe Leu Met Leu Leu Gln Asn Leu Lys
1190 1195 1200
Leu Gly Asp Asp Gln Tyr Val Arg Ser Gly Lys Asp His Val Ser
1205 1210 1215
Thr Leu Leu Thr Trp His Met His Lys Leu Val Glu Val Pro Phe
1220 1225 1230
Pro Val Val Asn Ala Met Met Lys Ser Tyr Val Lys Ser Lys Leu
1235 1240 1245
Lys Leu Leu Lys Gly Ser Gly Thr Thr Val Thr Glu Arg Ile Phe
1250 1255 1260
Arg Glu Tyr Phe Glu Met Gly Val Val Pro Ser His Ile Ser Ser
1265 1270 1275
Leu Ile Asp Met Gly Gln Gly Ile Leu His Asn Ala Ser Asp Phe
1280 1285 1290
Tyr Gly Leu Ile Ser Glu Arg Phe Ile Asn Tyr Cys Ile Gly Val
1295 1300 1305
Ile Phe Gly Glu Arg Pro Glu Ala Tyr Thr Ser Ser Asp Asp Gln
1310 1315 1320
Ile Thr Leu Phe Asp Lys Arg Leu Ser Asp Leu Val Asp Ser Asp
1325 1330 1335
Pro Glu Glu Val Leu Val Leu Leu Glu Phe His Ser His Leu Ser
1340 1345 1350
Gly Leu Leu Asn Lys Phe Ile Ser Pro Lys Ser Val Val Gly Arg
1355 1360 1365
Phe Ala Ala Glu Phe Lys Ser Arg Phe Tyr Val Trp Gly Glu Glu
1370 1375 1380
Val Pro Leu Leu Thr Lys Phe Val Ser Ala Ala Leu His Asn Val
1385 1390 1395
Lys Cys Lys Glu Pro His Gln Leu Cys Glu Thr Ile Asp Thr Ile
1400 1405 1410
Ala Asp Gln Ala Ile Ala Asn Gly Val Pro Val Phe Leu Val Asn
1415 1420 1425
Cys Ile Gln Arg Arg Thr Leu Asp Leu Leu Lys Tyr Ala Asn Phe
1430 1435 1440
Pro Leu Asp Pro Phe Leu Leu Asn Thr His Thr Asp Val Lys Asp
1445 1450 1455
Trp Leu Asp Gly Ser Arg Gly Tyr Arg Ile Gln Arg Leu Ile Glu
1460 1465 1470
Glu Leu Cys Pro Ser Glu Thr Lys Ile Met Arg Lys Leu Val Arg
1475 1480 1485
Arg Leu His His Lys Leu Lys Asn Gly Glu Cys Asn Glu Glu Phe
1490 1495 1500
Phe Leu Asp Leu Phe Asn Arg Glu Lys Lys Glu Ala Ile Leu Gln
1505 1510 1515
Leu Gly Glu Ile Leu Gly Leu Glu Asp Asp Leu Asn Glu Leu Ala
1520 1525 1530
Ser Ile Asn Trp Leu Asn Leu Asn Glu Met Phe Pro Leu Arg Met
1535 1540 1545
Val Leu Arg Gln Lys Val Val Tyr Pro Ser Val Met Thr Phe Gln
1550 1555 1560
Glu Glu Lys Ile Pro Ser Leu Ile Lys Thr Leu Gln Asn Lys Leu
1565 1570 1575
Cys Ser Lys Phe Thr Arg Gly Ala Gln Lys Leu Leu Ser Glu Ala
1580 1585 1590
Ile Asn Lys Ser Ala Phe Gln Ser Cys Val Ser Ser Gly Phe Ile
1595 1600 1605
Gly Leu Cys Lys Thr Leu Gly Ser Arg Cys Val Arg Asn Lys Asn
1610 1615 1620
Arg Glu Asn Met Tyr Ile Arg Lys Val Leu Glu Asp Leu Thr Met
1625 1630 1635
Asp Glu His Val Thr Arg Val His Lys Gln Asp Gly Val Met Leu
1640 1645 1650
Tyr Ile Cys Asp Lys Gln Arg His Pro Glu Ala His Arg Asp His
1655 1660 1665
Ile Asn Leu Leu Arg Pro Leu Leu Trp Asp Tyr Ile Cys Ile Ser
1670 1675 1680
Leu Ser Asn Ser Phe Glu Leu Gly Val Trp Val Leu Ala Glu Pro
1685 1690 1695
Val Lys Gly Lys Asn Glu Ser Asn Ser Ala Val Arg His Leu Asn
1700 1705 1710
Pro Cys Asp Tyr Val Ala Arg Lys Pro Glu Ser Ser Arg Leu Leu
1715 1720 1725
Glu Asp Lys Val Ser Leu Asn His Val Ile Gln Ser Val Arg Arg
1730 1735 1740
Leu Tyr Pro Lys Ile Phe Glu Asp Gln Leu Leu Pro Phe Met Ser
1745 1750 1755
Asp Val Ser Ser Lys Asn Met Arg Trp Ser Pro Arg Ile Lys Phe
1760 1765 1770
Leu Asp Leu Cys Val Leu Ile Asp Ile Asn Ser Glu Ser Leu Ser
1775 1780 1785
Leu Ile Ser His Val Val Lys Trp Lys Arg Asp Glu His Tyr Thr
1790 1795 1800
Val Leu Phe Ser Asp Leu Val Asn Ser His Gln Arg Ser Asp Ser
1805 1810 1815
Ser Leu Val Asp Glu Phe Val Val Ser Thr Arg Asp Val Cys Lys
1820 1825 1830
Asn Phe Leu Lys Gln Val Tyr Phe Glu Ser Phe Val Arg Glu Phe
1835 1840 1845
Val Ala Thr Ala Arg Thr Leu Gly Asn Phe Ser Trp Phe Pro His
1850 1855 1860
Lys Asp Met Met Pro Ser Glu Asp Gly Ala Glu Ala Leu Gly Pro
1865 1870 1875
Phe Gln Ser Phe Ile Leu Lys Val Val Asn Lys Lys Ile Glu Arg
1880 1885 1890
Pro Met Phe Arg Asn Asp Leu Gln Phe Gly Phe Gly Trp Phe Ser
1895 1900 1905
Tyr Arg Val Gly Asp Val Val Cys Asn Ala Ala Met Leu Ile Lys
1910 1915 1920
Gln Gly Leu Thr Asp Pro Lys Ala Phe Lys Ser Leu Arg Asp Leu
1925 1930 1935
Trp Asp Tyr Met Leu Ser Ser Thr Glu Gly Ile Leu Glu Phe Ser
1940 1945 1950
Ile Thr Val Asp Phe Thr His Asn Gln Asn Asn Thr Asp Cys Leu
1955 1960 1965
Arg Lys Phe Ser Leu Ile Phe Val Val Lys Cys Gln Leu Gln Ser
1970 1975 1980
Pro Gly Val Ala Asp Tyr Leu Ser Cys Ser His Phe Phe Lys Gly
1985 1990 1995
Glu Val Asp Arg Arg Leu Leu Asp Glu Cys Leu Asn Leu Leu Arg
2000 2005 2010
Thr Asp Pro Ile Phe Lys Ala Asn Asp Gly Val Phe Asp Ile Arg
2015 2020 2025
Ser Glu Glu Phe Glu Asp Tyr Met Glu Asp Pro Leu Thr Leu Gly
2030 2035 2040
Asp Ser Leu Glu Leu Glu Leu Ile Gly Ser Arg Arg Ile Leu Asn
2045 2050 2055
Glu Ile Lys Ser Thr Asp Phe Glu Arg Ile Gly Pro Glu Trp Glu
2060 2065 2070
Pro Val Pro Leu Thr Ile Arg Lys Gly Ala Leu Phe Glu Gly Arg
2075 2080 2085
Asn Phe Val Gln Asn Ile Ser Val Lys Leu Glu Thr Lys Asp Met
2090 2095 2100
Arg Val Phe Leu Ala Glu Leu Glu Gly Cys Gly Glu Ile Gly Asp
2105 2110 2115
Val Leu Gly Ser Leu Leu Leu His Arg Phe Arg Thr Gly Glu His
2120 2125 2130
Leu Met Glu Ser Glu Ile Ser Thr Val Leu Gln Glu Leu Cys Met
2135 2140 2145
Asp Arg Ser Val Met Leu Thr Pro Leu Ser Phe Val Pro Asp Trp
2150 2155 2160
Phe Thr Phe Arg Asp Cys Arg Leu Cys Phe Ser Arg Ser Lys Asn
2165 2170 2175
Thr Val Met Tyr Glu Thr Thr Gly Gly Arg Phe Arg Leu Lys Gly
2180 2185 2190
Lys Ser Cys Asp Asp Trp Leu Ala Glu Arg Val Ala Glu Glu Ile
2195 2200 2205
Asp
- 用于制备抗肿瘤沙粒病毒的方法以及沙粒病毒突变体
- 用于治疗和/或预防肿瘤的沙粒病毒和用于制备具有(改善的)肿瘤消退性能的沙粒病毒的方法