CN101688197A - Hcv基因 - Google Patents
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Abstract
本发明提供丙型肝炎病毒基因、来自该基因的复制子RNA、导入了复制子RNA的复制子复制细胞、以及使用了该复制子复制细胞的药物的筛选方法。通过将含有下述(A)、(B)、(C)、(D)或(E)的多核苷酸的复制子RNA、或含有编码丙型肝炎病毒的多蛋白氨基酸序列中第1804位的亮氨酸和第1966位的赖氨酸的核苷酸以及编码NS4B蛋白的多核苷酸的基因型1b的复制子RNA导入细胞中，可以制作复制子复制细胞，利用该复制子复制细胞可以进行药物的筛选。所述(A)～(E)的多核苷酸为：(A)包含SEQ ID NO：5所示的核苷酸序列的多核苷酸；(B)包含SEQ ID NO：7所示的核苷酸序列的多核苷酸；(C)编码包含SEQ ID NO：6所示的氨基酸序列的多肽的多核苷酸；(D)编码包含SEQID NO：8所示的氨基酸序列的多肽的多核苷酸；(E)包含与SEQ ID NO：5或SEQ ID NO：7所示的核苷酸序列的同源性为90％以上的核苷酸序列的多核苷酸。
Description
技术领域
本发明涉及丙型肝炎病毒(以下有时称作“HCV”)基因、来自该基因的复制子RNA、导入了复制子RNA的复制子复制细胞、以及使用了该复制子复制细胞的药物的筛选方法。
背景技术
HCV是丙型慢性肝炎的致病因子，根据WHO的统计，推测全球有1.7亿感染者。HCV是分类为黄病毒科、黄病毒属的病毒，认为其经由血液或血液成分而感染，在肝脏中增殖。虽然HCV感染者在感染初期仅出现较轻微的症状，但往往会转为慢性，经过一定期间的无症候性期后，发展为慢性肝炎。而且，随着长期感染，病情向肝硬化发展，往往会发展为肝癌。认为肝癌中有95％与肝炎病毒有关，而其中的80％是由HCV感染引起的。
在丙型慢性肝炎的治疗中广泛使用干扰素。近年来，通过改良干扰素的剂型、以及改善干扰素与利巴韦林联用疗法等给药方法，HCV从体内被驱除、治愈的比例也逐渐增加。但通过给予干扰素而得到的治愈率才50％左右，认为存在多种对干扰素治疗显示出抵抗性的HCV。因此，人们希望开发对干扰素抵抗性病毒具有治疗效果的药物。
在上述药物的开发中，药物的筛选系统是必需的。虽然有人报道了使HCV在试管内感染来自人或猴的细胞并使其增殖，但上述增殖系统的感染效率、增殖效率均低，无法用作药物的筛选系统。
最近，脇田等人从丙型重症肝炎患者体内分离出基因型2a的HCV基因(专利文献1)。在试管内(体外)由上述分离的JFH1株合成全长RNA，并导入来自人肝癌的细胞(Huh7细胞)中时，可以得到在细胞内自主复制的复制子RNA。并且，确认感染性微粒被排放到导入有复制子RNA的细胞的培养上清中(非专利文献1)。因此，通过将JFH1株的复制子RNA导入来自人肝癌的细胞(Huh7细胞)中，并将得到的感染性微粒再次与来自人肝癌的细胞进行培养，可以建立再感染增殖系统。通过使用该再感染增殖系统，开始了抗HCV药物的筛选。
但是，JFH1株为基因型2a的HCV，是干扰素感受性的HCV。因此，不具有对干扰素显示出抵抗性的HCV基因区，也无法特定在规定干扰素抵抗性的区域发挥作用的宿主侧的因子。因此，有可能无法筛选对干扰素抵抗性的HCV有效的药物。
最近，Lemon等人报道了将基因型1a的H77株的复制子RNA导入来自人肝癌的细胞(Huh7细胞)中的感染增殖系统(非专利文献2)。但是，虽然使由导入了该复制子RNA的细胞的培养上清得到的病毒颗粒再次感染来自人肝癌的细胞，但与上述JFH1株的感染性颗粒相比，感染效价低约400倍，由此认为H77株的复制子RNA释放了失去感染性的病毒颗粒。因此认为：可在试管内复制的H77株的RNA复制子失去了产生感染性颗粒的功能，并未保持本来的HCV的增殖功能。
因此，使用了该H77的复制子RNA的感染增殖系统的筛选系统有可能无法筛选对在机体内具有增殖功能的HCV有效的药物。
如上所述，由于HCV不存在高效率的试管内培养系统，所以难以进行对HCV治疗有用的药物的筛选。例如，对于目前广泛用于HCV治疗的干扰素，是以患者为受试体开发和改良了直接疗法，对患者造成很大的负担。上述脇田和Lemon所报道的复制子RNA虽然可以筛选一部分药物，但这些复制子RNA存在上述问题，认为其无法筛选可广泛用于HCV治疗的药物。
专利文献1：日本特开2002-171978号公报
非专利文献1：Nature Medicine，(美国)2005年，第11卷，第791～796页
非专利文献2：Proceeding of the National Academy of Science of theUnited State of America，2006年，第103卷，第2310～2315页
发明内容
发明所要解决的课题
本发明人等为了得到可广泛用于HCV治疗的药物，对HCV的高效率增殖系统、特别是对具有基因型1b型的基因、呈干扰素抵抗性、可产生感染性颗粒的试管内增殖系统进行了深入研究。首先，从重症化肝炎患者的血清中分离出全长HCV基因，确定了具有9594碱基的核苷酸序列的SEQ ID NO：1的全核苷酸序列。由该HCV基因制作复制子RNA，并将其导入来自人肝癌的细胞中时，确认该复制子RNA在细胞内自主增殖，可以进行RNA的复制。进一步发现：通过向该复制子RNA的NS4B蛋白区导入2个氨基酸序列的突变，RNA的复制效率显著提高，许多病毒颗粒被释放到培养上清中。之后，通过将该HCV颗粒再次与来自人肝癌的细胞进行培养，可以建立再感染增殖系统。进一步发现：使用了该复制子复制细胞和感染性颗粒的再感染增殖系统作为HCV治疗用药物的筛选系统、特别是作为对干扰素抵抗性病毒的药物的筛选系统是有用的。
本发明基于上述知识而完成。
解决课题的方法
因此，本发明涉及丙型肝炎病毒基因，该基因含有选自下述(A)～(F)的多核苷酸：
(A)包含SEQ ID NO：5所示的核苷酸序列的多核苷酸；
(B)包含SEQ ID NO：7所示的核苷酸序列的多核苷酸；
(C)包含SEQ ID NO：65所示的核苷酸序列的多核苷酸；
(D)编码包含SEQ ID NO：6所示的氨基酸序列的多肽的多核苷酸；
(E)编码包含SEQ ID NO：8所示的氨基酸序列的多肽的多核苷酸；以及
(F)编码包含SEQ ID NO：66所示的氨基酸序列的多肽的多核苷酸。
在本发明的丙型肝炎病毒基因的优选方式中，所述丙型肝炎病毒基因为：包含SEQ ID NO：1、SEQ ID NO：3、SEQ ID NO：10、SEQ IDNO：61或SEQ ID NO：63所示的核苷酸序列的多核苷酸。
另外，本发明涉及基因型1b的丙型肝炎病毒基因，该基因含有编码丙型肝炎病毒的多蛋白的氨基酸序列中第1804位的亮氨酸和第1966位的赖氨酸的核苷酸和编码NS4B蛋白的多核苷酸。
本发明还涉及DNA，该DNA包括在包含上述丙型肝炎病毒基因的核苷酸序列中尿苷置换成胸腺嘧啶的核苷酸序列的单链DNA。
本发明还涉及多肽，该多肽包含SEQ ID NO：6、SEQ ID NO：8或SEQ ID NO：66所示的氨基酸序列。
并且，本发明还涉及丙型肝炎病毒多蛋白，其中NS4B区的肽为包含SEQ ID NO：6、SEQ ID NO：8或SEQ ID NO：66所示的氨基酸序列的多肽。
本发明还涉及丙型肝炎病毒蛋白，该蛋白为选自包含SEQ ID NO：2、SEQ ID NO：4、SEQ ID NO：11、SEQ ID NO：62或SEQ ID NO：64所示的氨基酸序列中第1位～第191位氨基酸序列的核心蛋白、包含第192位～第383位氨基酸序列的E1蛋白、包含第384位～第746位氨基酸序列的E2蛋白、包含第747位～第809位氨基酸序列的P7蛋白、包含第810位～第1026位氨基酸序列的NS2蛋白、包含第1027位～第1657位氨基酸序列的NS3蛋白、包含第1658位～第1711位氨基酸序列的NS4A蛋白、包含第1712位～第1972位氨基酸序列的NS4B蛋白、包含第1973位～第2419位氨基酸序列的NS5A蛋白、包含第2420位～第3010位氨基酸序列的NS5B蛋白中的至少一种。
本发明还涉及复制子RNA，该复制子RNA包括选自下述(A)～(G)的多核苷酸：
(A)包含SEQ ID NO：5所示的核苷酸序列的多核苷酸；
(B)包含SEQ ID NO：7所示的核苷酸序列的多核苷酸；
(C)包含SEQ ID NO：65所示的核苷酸序列的多核苷酸；
(D)编码包含SEQ ID NO：6所示的氨基酸序列的多肽的多核苷酸；
(E)编码包含SEQ ID NO：8所示的氨基酸序列的多肽的多核苷酸；
(F)编码包含SEQ ID NO：66所示的氨基酸序列的多肽的多核苷酸；以及
(G)包含与SEQ ID NO：5、SEQ ID NO：7或SEQ ID NO：65所示的核苷酸序列的同源性为90％以上的核苷酸序列的多核苷酸。
另外，本发明涉及基因型1b的复制子RNA，该复制子RNA包括：编码丙型肝炎病毒的多蛋白的氨基酸序列中第1804位的亮氨酸和第1966位的赖氨酸的核苷酸；以及编码NS4B蛋白的多核苷酸。
在本发明的复制子RNA的优选方式中，所述复制子RNA包括：
(A)丙型肝炎病毒的5’非翻译区的第1位～第341位的多核苷酸、编码丙型肝炎病毒的多蛋白中第1027位～第3010位多肽的多核苷酸、以及3’非翻译区的多核苷酸；或
(B)5’非翻译区的第1位～第341位的多核苷酸、编码包含3010个氨基酸的丙型肝炎病毒的多蛋白的多核苷酸、以及3’非翻译区的多核苷酸。
在本发明的复制子RNA的优选方式中，所述复制子RNA为干扰素抵抗性。
在本发明的复制子RNA的另一优选方式中，所述复制子RNA包括：
(A)包含SEQ ID NO：1所示的核苷酸序列中第1位～第341位的核苷酸序列的多核苷酸和包含SEQ ID NO：1所示的核苷酸序列中第3420位～第9594位的核苷酸序列的多核苷酸；
(B)包含SEQ ID NO：3所示的核苷酸序列中第1位～第341位的核苷酸序列的多核苷酸和包含SEQ ID NO：3所示的核苷酸序列中第3420位～第9594位的核苷酸序列的多核苷酸；
(C)包含SEQ ID NO：10所示的核苷酸序列中第1位～第341位的核苷酸序列的多核苷酸和包含SEQ ID NO：10所示的核苷酸序列中第3420位～第9594位的核苷酸序列的多核苷酸；
(D)包含SEQ ID NO：61所示的核苷酸序列中第1位～第341位的核苷酸序列的多核苷酸和包含SEQ ID NO：61所示的核苷酸序列中第3420位～第9594位的核苷酸序列的多核苷酸；
(E)包含SEQ ID NO：63所示的核苷酸序列中第1位～第341位的核苷酸序列的多核苷酸和包含SEQ ID NO：63所示的核苷酸序列中第3420位～第9594位的核苷酸序列的多核苷酸；
(F)包含相对于SEQ ID NO：1所示的核苷酸序列中第1位～第341位的核苷酸序列为90％以上的同源性的核苷酸序列的多核苷酸和包含与SEQ ID NO：1所示的核苷酸序列中第3420位～第9594位的核苷酸序列的同源性为90％以上的核苷酸序列的多核苷酸；
(G)包含相对于SEQ ID NO：3所示的核苷酸序列中第1位～第341位的核苷酸序列为90％以上的同源性的核苷酸序列的多核苷酸、和包含与SEQ ID NO：3所示的核苷酸序列中第3420位～第9594位的核苷酸序列的同源性为90％以上的核苷酸序列的多核苷酸；
(H)包含相对于SEQ ID NO：10所示的核苷酸序列中第1位～第341位的核苷酸序列为90％以上的同源性的核苷酸序列的多核苷酸、和包含与SEQ ID NO：10所示的核苷酸序列中第3420位～第9594位的核苷酸序列的同源性为90％以上的核苷酸序列的多核苷酸；
(I)包含相对于SEQ ID NO：61所示的核苷酸序列中第1位～第341位的核苷酸序列为90％以上的同源性的核苷酸序列的多核苷酸、和包含与SEQ ID NO：61所示的核苷酸序列中第3420位～第9594位的核苷酸序列的同源性为90％以上的核苷酸序列的多核苷酸；或
(J)包含相对于SEQ ID NO：63所示的核苷酸序列中第1位～第341位的核苷酸序列为90％以上的同源性的核苷酸序列的多核苷酸、和包含与SEQ ID NO：63所示的核苷酸序列中第3420位～第9594位的核苷酸序列的同源性为90％以上的核苷酸序列的多核苷酸。
在本发明的复制子的另一优选方式中，上述复制子RNA为：包含SEQ ID NO：1、SEQ ID NO：3、SEQ ID NO：10、SEQ ID NO：61或SEQ ID NO：63所示的核苷酸序列的多核苷酸；或包含与SEQ ID NO：1、SEQ ID NO：3、SEQ ID NO：10、SEQ ID NO：61或SEQ ID NO：63所示的核苷酸序列的同源性为90％以上的核苷酸序列的多核苷酸。
并且，在本发明的复制子的另一优选方式中，所述复制子包括至少一个选择标记基因或报道基因和至少一个IRES序列。
本发明还涉及编码上述复制子RNA的DNA。
本发明还涉及包含上述DNA的载体。
本发明还涉及复制子复制细胞，该复制子复制细胞是通过将选自上述复制子RNA、上述DNA和上述载体的至少一种导入到细胞中而制作的。
在本发明的复制子复制细胞的优选方式中，上述细胞为来自肝细胞的细胞，优选上述来自肝细胞的细胞为Huh-7细胞。
本发明还涉及复制子RNA，该复制子RNA由上述复制子复制细胞产生。
并且，本发明涉及丙型肝炎病毒蛋白，该蛋白为选自由上述复制子复制细胞产生的CORE、E1、E2、P7、NS2、NS3、NS4A、NS4B、NS5A和NS5B中的至少一种。
本发明还涉及丙型肝炎病毒颗粒，该颗粒由复制子复制细胞产生。
本发明还涉及筛选方法，其是筛选控制丙型肝炎病毒感染的物质的方法，该方法包括：使上述复制子复制细胞与上述物质接触的步骤；以及分析复制子RNA的增加度的步骤。
在本发明的筛选方法的优选方式中，上述分析复制子RNA增加度是指检测复制子RNA或丙型肝炎病毒蛋白。
在本说明书中，“复制子RNA”是指根据病毒RNA制作的、在细胞内具有自主复制能力的RNA，只要能够引起RNA的复制，可以包括能够产生病毒颗粒的物质，也可以包括不能产生病毒颗粒的物质。
在本说明书中，“干扰素抵抗性”是指在试管内和机体内通过给予干扰素，HCV的复制或增殖没有被显著抑制。
发明效果
利用本发明的HCV基因，可以在试管内分析能够在机体内复制的HCV基因。通过利用该HCV基因，可以制作本发明的RNA复制子。并且，利用导入了上述RNA复制子的复制子复制细胞，可以进行抗HCV药物的筛选。由本发明的HCV基因制作的复制子RNA是基因型1b的干扰素抵抗性的RNA复制子。另外，可以由导入了该复制子RNA的复制子复制细胞产生感染性病毒颗粒。因此，可以提供与基因型1b且为干扰素抵抗性的HCV在机体内的增殖机理相同的试管内模型。而且，通过利用该HCV的增殖模型，可以进行可抑制肝炎重症化的药物的筛选和药品的开发。
附图简述
图1显示通过将本发明的复制子RNA导入到细胞中而产生核心蛋白。通过电穿孔将pTPF1和pTPF1/4B导入Huh-7细胞中，于4、24、48和72小时后测定培养上清中核心蛋白的浓度。
图2显示由本发明的复制子复制细胞产生的感染颗粒对细胞的再感染。感染后，于4、24、48、72和96小时后测定培养上清中核心蛋白的浓度。
图3显示使用本发明的筛选方法，环孢菌素A对核心蛋白的产生的抑制效果。在添加环孢菌素A和作为对照的未添加环孢菌素A的情况下导入复制子RNA，于4、24、48和72小时后测定培养上清中核心蛋白的浓度。
图4显示通过将本发明的复制子RNA导入到细胞中而产生核心蛋白。通过电穿孔将pAHC1和pAHC/4Bm导入Huh-7细胞中，于4、24、48和72小时后测定培养上清中核心蛋白的浓度。
实施发明的最佳方式
以下阐述本发明的最佳方式，但本发明并不限于该方式。
本发明的丙型肝炎病毒基因只要是属于基因型1b的HCV基因即可，对其没有限定，但优选包括本发明的编码NS4B蛋白的多核苷酸。另外，优选显示干扰素抵抗性的HCV基因。
HCV基因根据其核苷酸序列，至少可以分为6种基因型。其中属于基因型1的HCV进一步分为基因型1a和基因型1b。具体而言，基因型1b的基因型包括具有多核苷酸的HCV，所述多核苷酸包含相对于SEQ ID NO：5或7的核苷酸序列显示出90％以上的同源性的核苷酸序列。
作为本发明的NS4B蛋白，可以列举出：包含SEQ ID NO：6、SEQID NO：8或SEQ ID NO：66所示的氨基酸序列的多肽。丙型肝炎病毒基因在5’非翻译区(5’UTR)与3’非翻译区(3’UTR)之间包含编码病毒的结构蛋白-核心蛋白、E1蛋白、E2蛋白和非结构蛋白-P7蛋白、NS2蛋白、NS3蛋白、NS4A蛋白、NS4B蛋白、NS5A蛋白、NS5B蛋白的区域。丙型肝炎病毒基因感染后在宿主细胞内发挥mRNA的功能，合成一长约3000个氨基酸的多蛋白。之后，被宿主的信号肽酶、信号肽肽酶和HCV基因组所编码的蛋白酶切断，产生上述3种结构蛋白和7种非结构蛋白。
上述10种HCV蛋白中，认为NS4B蛋白与NS3～NS5B的其他非结构蛋白形成复合体，再与宿主蛋白一起形成RNA复制复合体，进行基因组RNA的复制，在病毒的复制中发挥重要作用。编码于由重症肝炎患者取得的HCV基因的NS4B区的、包含本发明的SEQ ID NO：6所示的氨基酸序列的多肽(以下称作TPF1-NS4B多肽)、包含SEQ IDNO：8所示的氨基酸序列的多肽(以下称作TPF1-突变NS4B多肽)和包含SEQ ID NO：66所示的氨基酸序列的多肽(以下有时称作AHC1-突变NS4B多肽)、特别是TPF1-突变NS4B多肽和AHC1-突变NS4B多肽参与HCV基因的复制，显示出显著效果。
因此，本发明的丙型肝炎病毒基因优选包括编码TPF1-NS4B多肽或TPF1-突变NS4B多肽的多核苷酸，更优选包括包含SEQ ID NO：5所示的核苷酸序列的多核苷酸(以下称作TPF1-NS4B多核苷酸)，最优选包括包含SEQ ID NO：7所示的核苷酸序列的多核苷酸(TPF1-突变NS4B多核苷酸)或包含SEQ ID NO：65所示的核苷酸序列的多核苷酸(AHC1-突变NS4B多核苷酸)。但本发明的丙型肝炎病毒基因只要参与HCV基因的复制并显示出显著效果即可，并不限于这些，可以列举如：含有多核苷酸的丙型肝炎病毒基因，所述多核苷酸包含相对于SEQ ID NO：5、SEQ ID NO：7或SEQ ID NO：65所示的核苷酸序列优选为90％以上、更优选为95％以上、进一步优选为97％以上、更进一步优选为99％以上的同源性的核苷酸序列。
对本发明的丙型肝炎病毒基因没有限定，只要包括NS4B区的多核苷酸即可，可以包括含有HCV的部分多核苷酸的部分丙型肝炎病毒基因和包含全长HCV多核苷酸的丙型肝炎病毒基因。作为HCV的部分多核苷酸，可以列举如：包含SEQ ID NO：1、3、10、61或63中的任意核苷酸序列部分的核苷酸，具体可以列举：5’UTR(第1位～第341位的核苷酸序列)、核心(第342位～第914位的核苷酸序列)、E1区(第915位～第1490位的核苷酸序列)、E2区(第1491位～第2579位的核苷酸序列)、P7区(第2580位～第2768位的核苷酸序列)、NS2区(第2769位～第3419位的核苷酸序列)、NS3区(第3420位～第5312位的核苷酸序列)、NS4A区(第5313位～第5474位的核苷酸序列)、NS4B区(第5475位～第6257位的核苷酸序列)、NS5A区(第6258位～第7598位的核苷酸序列)、NS5B区(第7599位～第9371位的核苷酸序列)、3’非翻译区(第9372位～第9594位的核苷酸序列)的部分多核苷酸。另外，作为包含全长HCV多核苷酸的丙型肝炎病毒基因，可以列举出：包含SEQ ID NO：1、SEQ ID NO：3、SEQ ID NO：10、SEQ ID NO：61或SEQ ID NO：63所示的核苷酸序列的丙型肝炎病毒基因。
本发明的丙型肝炎病毒基因包括从重症肝炎患者体内分离的丙型肝炎病毒基因。重症肝炎是指肝炎中症状出现后8周以内呈现II度以上的脑症和凝血酶原时间为40％以下，分为10日以内出现脑症的急性型和10日以后出现脑症的亚急性型。
本发明的丙型肝炎病毒基因的克隆可如下进行。采用酸性异硫氰酸胍·苯酚·氯仿法(例如ISOGEN-LS、日本ジ一ン公司制备)等，由重症丙型肝炎患者的血清制备总RNA。通过使用3’UTR特异性引物和小鼠白血病病毒逆转录酶(Superscript II、Life technologies公司制备)的逆转录反应，由总RNA合成cDNA。
通过使用5’UTR～3’UTR的特异性引物的PCR[PCR Protocols，Academic Press(1990)]来扩增所合成的HCV的cDNA。将所扩增的HCV基因克隆到pGEM-T EASY载体(Promega公司制备)中，确定核苷酸序列。
HCV基因的两末端可以通过使用5’UTR特异性引物的5’-RACE和使用3’UTR特异性引物的3’-RACE[Proc.Natl.Acad.Sci.USA，85，8998(1988)]而得到。将得到的cDNA片段连起来，可以获得全长HCV基因。
对本发明的DNA没有限定，只要是相当于作为RNA的上述丙型肝炎病毒基因的DNA即可，可以列举如：利用逆转录酶由丙型肝炎病毒基因合成的单链cDNA以及包含该单链cDNA和其互补链的双链DNA。
本发明的多肽只要是编码于包含SEQ ID NO：1、3、10、61或63所示的核苷酸序列的多核苷酸中的多肽、或者是包括丙型肝炎病毒的多蛋白的氨基酸序列中第1804位的亮氨酸和第1966位的赖氨酸的多肽即可，对其区域及长度没有特别限定，但优选为包含SEQ ID NO：6、SEQ ID NO：8或SEQ ID NO：66所示的氨基酸序列的多肽。
本发明的丙型肝炎病毒蛋白可以包括：包含SEQ ID NO：2、4、11、62或64所示的氨基酸序列中第1位～第191位的氨基酸序列的核心蛋白、包含第192位～第383位的氨基酸序列的E1蛋白、包含第384位～第746位的氨基酸序列的E2蛋白、包含第747位～第809位的氨基酸序列的P7蛋白、包含第810位～第1026位的氨基酸序列的NS2蛋白、包含第1027位～第1657位的氨基酸序列的NS3蛋白、包含第1658位～第1711位的氨基酸序列的NS4A蛋白、包含第1712位～第1972位的氨基酸序列的NS4B蛋白、包含第1973位～第2419位的氨基酸序列的NS5A蛋白、或包含第2420位～第3010位的氨基酸序列的NS5B蛋白。
本发明的复制子RNA只要是含有包含基因型1b的核苷酸序列的多核苷酸、在细胞内具有自主复制能力的RNA即可，没有特别限定。作为参与HCV的复制子RNA复制的核苷酸区，可以特别列举出：5’UTR、3’UTR和编码非结构蛋白-NS3蛋白、NS4A蛋白、NS4B蛋白、NS5A蛋白、NS5B蛋白的核苷酸区，在本发明的复制子RNA中，上述所有区都很重要，但在提高复制效率方面，编码NS4B蛋白的区是最重要的。特别是作为NS4B蛋白，优选作为包含SEQ ID NO：6所示的氨基酸序列的多肽的TPF1-NS4B多肽，更优选作为包含SEQID NO：8所示的氨基酸序列的多肽的TPF1-突变NS4B多肽、或者作为包含SEQ ID NO：66所示的氨基酸序列的多肽的AHC1-突变NS4B多肽。
因此，本发明的复制子RNA优选包括编码TPF1-NS4B多肽的多核苷酸、特别是包含SEQ ID NO：5所示的核苷酸序列的多核苷酸(TPF1-NS4B多核苷酸)的复制子RNA，更优选包括编码TPF1-突变NS4B多肽的多核苷酸、特别是包含SEQ ID NO：7所示的核苷酸序列的多核苷酸(TPF1-突变NS4B多核苷酸)、或编码AHC1-突变NS4B多肽的多核苷酸、特别是包含SEQ ID NO：65所示的核苷酸序列的多核苷酸(AHC1-突变NS4B多核苷酸)的复制子RNA。但本发明的复制子RNA并不限于上述包括NS4B区的多核苷酸的复制子RNA，还包括含有下述多核苷酸的复制子RNA，所述多核苷酸包含与SEQ ID NO：5、SEQ ID NO：7或SEQ ID NO：65所示的核苷酸序列的同源性优选为90％以上、更优选为95％以上、进一步优选为97％以上、最优选为99％以上的核苷酸序列。
TPF1-突变NS4B多核苷酸(SEQ ID NO：7)是指TPF1-NS4B多核苷酸(SEQ ID NO：5)的第278位的A置换成U、第763位的G被置换成A的多核苷酸。另外，TPF1-突变NS4B多肽(SEQ ID NO：8)是指TPF1-NS4B多肽(SEQ ID NO：6)的第93位的谷氨酰胺(Q)置换成亮氨酸(L)、第255位的谷氨酸(E)被置换成赖氨酸(K)的多肽。
作为本发明的丙型肝炎病毒基因和复制子RNA的一个实施方式，可以包括编码丙型肝炎病毒的多蛋白的氨基酸序列中第1804位的亮氨酸和第1966位的赖氨酸的核苷酸。
第1804位的亮氨酸和第1966位的赖氨酸的位置是指在包含3010个氨基酸的基因型1b的丙型肝炎病毒基因中的位置。
第1804位的亮氨酸和第1966位的赖氨酸是NS4B蛋白中所含的氨基酸，迄今为止含有上述氨基酸的NS4B蛋白还未见报道。因此，含有上述氨基酸的HCV多蛋白、含有编码上述氨基酸的多核苷酸的RNA复制子也未见报道。
对基因型1b的丙型肝炎病毒基因的核苷酸序列没有特别限定，例如包括与SEQ ID NO：1、SEQ ID NO：3、SEQ ID NO：10、SEQ ID NO：61、SEQ ID NO：63所示的核苷酸序列的同源性为90％以上的核苷酸序列。
本发明的复制子RNA的结构只要可以在细胞内复制即可，对其没有限定，可以列举出：包括丙型肝炎病毒的全长RNA的复制子RNA、或包括一部分RNA的亚基因组复制子RNA。例如，亚基因组复制子RNA可以包括：5’非翻译区(以下有时称作5’UTR)、3’非翻译区(以下有时称作3’UTR)和编码非结构蛋白-NS3蛋白、NS4A蛋白、NS4B蛋白、NS5A蛋白、NS5B蛋白的核苷酸区，优选可以包括：包含SEQ ID NO：1、SEQ ID NO：3、SEQ ID NO：61或SEQ ID NO：63所示的核苷酸序列中第1位～第341位的核苷酸序列的多核苷酸、以及包含SEQ ID NO：1、SEQ ID NO：3、SEQ ID NO：61或SEQ ID NO：63所示的核苷酸序列中第3420位～第9594位的核苷酸序列的多核苷酸。
在基因型1b的丙型肝炎病毒基因中，5’UTR通常包含341核苷酸，至于复制子RNA中所含的5’UTR，对其核苷酸序列没有限定，但优选包括其全长序列。就3’UTR而言，对其长度根据病毒株而不同，但通常包含41核苷酸的可变区、长度根据株而不同的多U区和98核苷酸的3’X区，至于复制子RNA中所含的3’UTR，其核苷酸序列及长度没有限定，但优选包括该株中的全长3’UTR。
本发明的复制子RNA除了包括全长RNA和亚基因组RNA以外，还可以包括筛选标记基因、报道基因或IRES序列，上述复制子RNA可以列举如：包含SEQ ID NO：9、SEQ ID NO：67或SEQ ID NO：68中记载的多核苷酸的复制子RNA。
作为筛选标记基因，可以列举如：抗生素耐性基因。在本发明中，优选的筛选标记基因的例子有：新霉素耐性基因、胸苷激酶基因、卡那霉素耐性基因、吡啶硫胺素耐性基因、腺苷酰转移酶基因、Zeocin耐性基因、嘌呤霉素耐性基因等，但优选新霉素耐性基因、胸苷激酶基因，最优选新霉素耐性基因。但本发明中的筛选标记基因并不限于这些。
作为报道基因，可以列举如：催化发光反应或显色反应的酶的结构基因。在本发明中，优选的报道基因的例子有：来自转座子Tn9的氯霉素乙酰转移酶基因、来自大肠杆菌的β葡糖醛酸酶或β半乳糖苷酶基因、萤光素酶基因、绿色萤光蛋白基因、来自水母的水母素(イクリオン，Aequorin)基因、分泌型胎盘碱性磷酸酶(SEAP)基因等。但本发明中的报道基因并不限于这些。
对IRES序列没有限定，可以列举如：EMCV IRES(脑心肌炎病毒的内部核糖体结合部位)、FMDV IRES、HCV IRES等，但更优选EMCV IRES和HCV IRES，最优选EMCV IRES。
本发明的复制子RNA优选为干扰素抵抗性。利用干扰素对HCV患者进行治疗时，干扰素是否有效，这要考虑例如病毒侧的因素和宿主侧的因素。病毒侧的因素可以列举出：对干扰素显示抵抗性的HCV基因区，但本发明的复制子RNA优选包括对干扰素显示抵抗性的HCV基因区的复制子RNA。对干扰素显示抵抗性的HCV基因区没有特别限定，可以列举如：被认为是NS5A区的IFN感受性指标的ISDR区。
本发明的复制子RNA优选包括基因型1b的核苷酸序列的多核苷酸的复制子RNA，可以列举如：含有包含与SEQ ID NO：5、SEQ ID NO：7或SEQ ID NO：65所示的核苷酸序列的同源性为90％以上的核苷酸序列的多核苷酸的RNA复制子。
对本发明的DNA没有限定，只要是直链状DNA的形态、且编码上述复制子RNA的DNA即可，例如还可以包括：用于产生复制子RNA的RNA启动子。
本发明的复制子RNA可以采用任意的基因工程学方法来制作。虽然没有限定，但复制子RNA例如可以利用以下方法进行制作。
利用常规方法将编码上述复制子RNA的DNA插入克隆载体中，制作DNA克隆。将该DNA插入RNA启动子的下游，制作可以产生复制子RNA的DNA克隆。优选上述RNA启动子为质粒克隆中所含的RNA启动子。对RNA启动子没有限定，可以列举出：T7RNA启动子、SP6RNA启动子、SP3RNA启动子，特别优选T7RNA启动子。
对插入DNA的载体没有特别限定，可以列举如：质粒载体、直链状双链DNA载体、以及腺病毒载体、腺病毒伴随病毒载体、逆转录病毒载体和慢病毒载体等病毒载体，但优选为质粒载体。
本发明的复制子RNA可以由上述插入有DNA的载体来制作。以DNA克隆为模板，利用RNA聚合酶合成RNA。RNA的合成可以利用常规方法从5’非翻译区开始。当模板DNA为质粒克隆时，还可以通过限制酶从该质粒克隆切出连接在RNA启动子下游的上述DNA区，使用其DNA片段作为模板来合成RNA。需要说明的是，优选所合成的RNA的3’末端与病毒基因组RNA的3’非翻译区一致，优选不添加其他序列也不删除其他序列。例如，在本发明的全长复制子RNA的一个优选方式中，将其插入到在5’UTR的上游具有T7RNA启动子、在3’UTR末端具有限制酶XbaI部位的载体中，经XbaI消化后，利用T7RNA聚合酶可以合成HCV基因组RNA。
本发明的复制子复制细胞可以通过将上述RNA复制子导入到任意的细胞中来制作。对导入复制子RNA的细胞没有特别限定，优选来自人肝脏的细胞、来自小鼠肝脏的细胞或来自猴肝脏的细胞，特别可以列举出：来自人肝癌的细胞-Huh7细胞、HepG2细胞或Hep3B细胞、或者IMY-N9细胞、HeLa细胞、CHO细胞、COS细胞、Vero细胞或293细胞。向细胞内导入复制子RNA可以利用任意的转染法来进行。上述导入法可以列举如：电穿孔法、粒子枪法、脂质转染法，但特别优选电穿孔法。
为了进行细胞内导入而使用含有选择标记基因或报道基因的复制子RNA时，利用选择标记基因或报道基因的表达，可以选择导入有该复制子RNA并持续进行复制的细胞。例如，当复制子RNA中含有新霉素耐性基因作为选择标记基因时，将转染了该复制子RNA的细胞播种在培养皿中，按0.05毫克/毫升～3.0毫克/毫升的浓度添加G418(新霉素)。之后，每周交换2次培养液继续培养，自播种时起2～3周后可以看到集落。
本发明的复制子复制细胞产生复制子RNA、丙型肝炎病毒蛋白和丙型肝炎病毒颗粒。因此，使用复制子复制细胞，可以产生复制子RNA、丙型肝炎病毒蛋白和丙型肝炎病毒颗粒。
在复制子复制细胞中复制的复制子RNA可以通过任意的RNA提取法从细胞内提取出来。从细胞中提取的RNA通过再次导入到细胞中，可以发挥复制子RNA的功能。本发明的丙型肝炎病毒蛋白可以使用分泌在细胞内或培养上清中的蛋白。所产生的丙型肝炎病毒蛋白可以通过公知的方法进行提取、纯化。另外，由复制子复制细胞产生的丙型肝炎病毒颗粒可以使用分泌在细胞内和培养上清中的病毒颗粒。本发明的丙型肝炎病毒蛋白和丙型肝炎病毒颗粒通过在复制子RNA中加入改变，以修饰RNA、病毒蛋白或病毒颗粒、降低病原性，从而还可用作疫苗。
通过使用上述复制子复制细胞，可以筛选控制丙型肝炎病毒感染的物质。“控制丙型肝炎病毒的感染”是指例如控制HCV RNA的复制(例如促进或抑制)、控制由RNA向蛋白质的翻译(例如促进或抑制)。
具体而言，使试验物质与复制子复制细胞接触，并分析复制子RNA的增加度，从而可以进行试验物质的筛选。复制子RNA的增加度是指复制子RNA的复制速度或量的变化。具体而言，通过检测或测定复制子细胞中的复制子RNA的量，并与对照的没有和被检物质接触的复制子复制细胞的复制子RNA的量进行比较，可以筛选被检物质。另外，通过检测或测定细胞中或上清中的丙型肝炎病毒蛋白的量，并与对照的没有和被检物质接触的复制子复制细胞的量进行比较，也可以筛选被检物质。对筛选中可以检测或测定的丙型肝炎病毒蛋白没有特别限定，但优选为核心蛋白，还可以使用市售的试剂盒来测定核心蛋白。另外，通过使筛选方法自动化，还可适应于高通量筛选(High-throughput Screening)方法。
并且，本发明的筛选方法作为评价所筛选的药物的效果的方法也有效。必需按照该筛选方法进行药物评价时，该筛选方法还可用作制造药物的方法。
《作用》
虽然关于包括编码丙型肝炎病毒的多蛋白的氨基酸序列中第1804位的亮氨酸和第1966位的赖氨酸的核苷酸的丙型肝炎病毒基因和复制子RNA并未完全阐明，但可作如下推论。但是，本发明并不限于以下的说明。
本发明人等使用编码其他3010个氨基酸的基因型1b的株代替后述的实施例9中使用的AHC1株，重复实施例9的操作，得到了与实施例9相同的结果。但是，作为具有NS4B蛋白以外的适应突变的亚基因组复制子，得到了下述复制子：碱基数第5308位的T突变为C，且3010个HCV多蛋白的第1656位的氨基酸由V(缬氨酸)突变为A(丙氨酸)的复制子；和除上述突变外，碱基数第6846位的A突变为G，且3010个HCV多蛋白的第2169位的氨基酸由T(酪氨酸)突变为A(丙氨酸)的复制子。
根据由TPF1株、AHC1株和上述基因型1b的株得到的实验结果，可以考虑以下情况。包括编码第1804位的亮氨酸和第1966位的赖氨酸的核苷酸的基因型1b的复制子RNA与不含该核苷酸的复制子RNA相比，RNA的复制效率提高。即，基因型1b的丙型肝炎病毒的复制子RNA通过具有上述两个适应突变，使RNA的复制效率提高。
通过使用上述的具有NS4B蛋白中的两个上述适应突变的复制子RNA，并转染到细胞中，确实可以得到复制子复制细胞。由该复制子复制细胞得到的复制子RNA除了NS4B蛋白中的两个上述适应突变之外，有时还导入有一个以上的其他适应突变。即，除了NS4B蛋白中的两个上述适应突变之外，有时通过导入一个以上的其他适应突变，复制子RNA的复制效率也会提高。
作为上述NS4B蛋白中的两个上述适应突变以外的适应突变，包括已知的适应突变和未知的适应突变。作为已知的适应突变，有人报道了表1所示的突变。
[表1]
实施例
《实施例1：重症丙型肝炎病毒全长基因的分离和解析》
(A)从血清中提取RNA
使用High Pure Viral Nucleic Acid Kit(Roche diagnosticscorporation)，按照生产商推荐的方法，从在重症肝炎患者的急性期采取的250μL血清中纯化RNA。
(B)cDNA的合成和通过PCR进行的cDNA的扩增
向已纯化的RNA中加入XR58R引物，利用SuperSucript II逆转录酶(Invitrogen公司)，按照生产商推荐的方法进行42℃、1小时的逆转录反应，得到cDNA。向所得反应液中加入RNaseH(Invitrogen)，使之在37℃下反应30分钟，分解RNA。使用HC-LongA1引物、1b9405R引物和Takara LA Taq DNA聚合酶(宝酒造)，对上述反应液进行聚合酶链反应(PCR)(以94℃、20秒、68℃、9分钟为一次热循环反应，重复进行30次热循环反应)，扩增cDNA。再使用HC85F和HC9302R引物，对所得的一部分反应液进行PCR，扩增HCV cDNA。
(C)cDNA的克隆
已扩增的DNA片段用0.7％琼脂糖凝胶通过电泳进行分离，使用QIAquick凝胶纯化试剂盒(QIAGEN公司)，按照生产商推荐的方法回收DNA片段。使回收的DNA片段与pGEM-T easy载体(Promega公司)发生连接反应，利用该质粒转化DH5α株。选择氨苄青霉素耐性转化体，用2YT培养基进行培养。使用Wizard Plus SV Miniprep DNA纯化系统从培养的菌体中纯化质粒。
(D)核苷酸序列的确定
HCV cDNA的核苷酸序列使用根据HCV的基因型1b的核苷酸序列设计的引物来确定。使用CEQ DTCS Quick Start试剂盒(ベツクマン·コ一ルタ一)，按照生产商推荐的方法进行反应，利用CEQ2000XLDNA分析系统(软件4.0.0版、ベツクマン·コ一ルタ一)进行分析。利用Sequencher(4.1.2版、Gene Codes Corporation)分析所得的数据。将得到的HCV克隆命名为pTPF1-0193。
(E)5’非翻译区的cDNA的获得和核苷酸序列的确定
再利用5’RACE法，由上述步骤(A)中得到的RNA获得5’非翻译区的末端cDNA。使用用于cDNA Ends快速扩增的5’RACE系统(System for Rapid Amplification of cDNA Ends)，2.0版(Invitrogen公司)试剂盒，按照附录的说明书进行实施。
用于cDNA合成的反义引物使用Chiba-as。使用SuperScript II逆转录酶(Invitrogen)来合成cDNA，并用S.N.A.P柱进行纯化，之后对cDNA进行TdT-tailing反应，添加dCTP。利用试剂盒中附带的5’RACE精简的锚定引物(Abridged Anchor Primer)和KY78引物，使用TakaraLA Taq DNA聚合酶(宝酒造)进行第一次PCR。以一部分该PCR产物为模板，利用试剂盒中附带的UTP引物和KM2引物，使用Takara LATaq DNA聚合酶(宝酒造)进行第二次PCR，得到PCR产物。将该PCR产物克隆到pGEM-T easy载体中，按照上述步骤(D)来确定核苷酸序列。将所得的包括SEQ ID NO：1中第1位～第709位的HCV cDNA克隆命名为pTPF1-0007。
(F)3’非翻译区的cDNA的获得和核苷酸序列的确定
利用3’RACE法，由上述步骤(A)中得到的RNA获得3’非翻译区的末端cDNA。首先，使用Poly(A)Tailing试剂盒(Ambion)，按照附录说明书向患者的RNA中添加Poly(A)。除了使用dT-Adp引物代替XR58R引物、使用3UTR-1F引物和Adp引物作为第一PCR的引物、以及使用XR58F和Adp引物作为第二PCR的引物以外，重复上述步骤(B)～(D)的操作。将得到的HCV cDNA克隆命名为pTPF1-8994。
将得到的HCV株命名为TPF1株。TPF1株是全长为9594碱基的HCV，其核苷酸序列见SEQ ID NO：1。所得TPF1株的多核苷酸在其342位～9374位之间具有编码一长3010个氨基酸的翻译区。TPF1株的多蛋白的氨基酸序列见SEQ ID NO：2。
以下显示用于克隆和确定核苷酸序列的引物。
XR58R(SEQ ID NO：12)：5’-tcatgcggct cacggacctt tcacagctag-3’
HClongA1(SEQ ID NO：13)：5’-atcgtcttca cgcagaaagc gtctagccat-3’
1b9405R(SEQ ID NO：14)：5′-gcctattggc ctggagtgtt tagctc-3’
HC85F(SEQ ID NO：15)：5′-atggcgttag tatgagtgtc gtgcagcct-3’
HC9302R(SEQ ID NO：16)：5’-tcgggcacga gacaggctgt gatatatgtc t-3’
chiba-as(SEQ ID NO：17)：5′-tgcacggtct acgagacct-3’
KY78(SEQ ID NO：18)：5’-ctcgcaagca ccctatcagc cagt-3’
KM2(SEQ ID NO：19)：5’-aggcattgag cgggtttat-3’
dT-Adp(SEQ ID NO：20)：5’-ctagactcga gtcgacatcg tttttttttt tttttttt-3’
3UTR-1F(SEQ ID NO：21)：5’-atcttagccc tagtcacggc-3’
Adp(SEQ ID NO：22)：5’-ctagactcga gtcgacatcg-3’
XR58F(SEQ ID NO：23)：5’-ctagctgtaa aggtccgtga gccgcatga-3’
M13Primer M3(SEQ ID NO：24)：5’-gtaaaacgac ggccagt-3’
M13Primer RV(SEQ ID NO：25)：5’-caggaaacag ctatgac-3’
104(SEQ ID NO：26)：5’-aggaagactt ccgagcggtc-3’
HC841S(SEQ ID NO：27)：5’-ggaacttgcc cggttgctct ttctctatct tc-3’
E1(SEQ ID NO：28)：5’-attccatggt ggggaactgg gctaa-3’
HC2069S(SEQ ID NO：29)：5’-taacaatacc ttgacctgcc ccacggactg-3’
HC2430S(SEQ ID NO：30)：5’-aacatcgtgg acgtgcaata cctgtacgg-3’
HC2461AS(SEQ ID NO：31)：5’-gaccctacac cgtacaggta-3’
HC2769S(SEQ ID NO：32)：5’-ttggaccggg agatggctgc atcgtg-3’
HC3632F(SEQ ID NO：33)：5’-cacccaaatg tacaccaatg t-3’
HC3928S(SEQ ID NO：34)：5’-tacccgttga gtctatggaa ac-3’
HC4016AS(SEQ ID NO：35)：5’-cacttggaat gtctgcggta-3’
HC4498S(SEQ ID NO：36)：5’-agggggggag gcatctcatt ttctg-3’
HC4888F(SEQ ID NO：37)：5’-tgctatgacg cgggctgtgc ttggta-3’
HC5381F(SEQ ID NO：38)：5’-ggtcattgtg ggcaggatca t-3’
HC5692S(SEQ ID NO：39)：5’-ctgcctggaa accccgcgat-3’
HC5858F(SEQ ID NO：40)：5’-tggcagcata ggccttggga aggt-3’
HC6315F(SEQ ID NO：41)：5’-aagacctggc tccagtccaa g-3’
5A-1(SEQ ID NO：42)：5’-ttccatgctc accgacccct c-3’
HC7090S(SEQ ID NO：43)：5’-gtggagtcag agaataaggt-3’
HC7743F(SEQ ID NO：44)：5’-cagaagaagg tcacctttgac-3’
HC8192S(SEQ ID NO：45)：5’-gcagcgggtc gagttcctgg tgaat-3’
HC8939F(SEQ ID NO：46)：5’-ctacggggcc tgttactcca ttgaac-3’
《实施例2：亚基因组RNA复制子的制作》
将丙型肝炎病毒TPF1株的全长多核苷酸插入pBluescriptIISK(+)的T7RNA启动子序列的下游(以下称作pTPF1)。
接下来，将pTPF1的编码结构蛋白的区和编码非结构蛋白的区的一部分替换成新霉素耐性基因(新霉素磷酸转移酶、NPT-II)和EMCV-IRES(脑心肌炎病毒的内部核糖体结合部位)，建立质粒DNApRepTPF1。其建立顺序遵照已经报道的顺序(Lohmann等，Science，(1999)285，第110～113页)。
具体而言，首先将pTPF1用限制酶AgeI和BsrGI切断，在该切断部位连接插入以下片段：将来自pTPF1的5’UTR～核心区的序列和来自pcDNA3.1(+)的新霉素耐性基因通过PCR扩增进行扩增，并用限制酶AgeI和PmeI切断而得到的片段；以及将EMCV-IRES～NS3区的序列通过PCR扩增进行结合，并用限制酶PmeI和BsrGI切断而得到的片段。以将该质粒DNA pRepTPF1用XbaI切断的产物为模板，使用Megascript T7试剂盒(Ambion)来合成RNA。按照生产商推荐的方法纯化RNA。
向Dulbecco’s改进的Eagle培养基(D-MEM，IWAKI)中加入10％胎牛血清(FBS)，并加入青霉素和链霉素，使分别达到50U/mL和50μg/mL的浓度，以所得培养基作为培养液，添加5％二氧化碳，在37℃下培养人肝癌细胞(Huh7、JCRB0403)。将形成融合之前的细胞通过胰蛋白酶、EDTA处理，从培养皿上剥离，并再悬浮于添加了血清的培养基中，从而使胰蛋白酶失活。用PBS清洗2次，之后再悬浮于添加有1.25％DMSO的Cytomix(120mM氯化钾、10mM磷酸钾、5mM氯化镁、25mM HEPES、0.15mM氯化钙、2mM EGTA、pH7.6)中，之后移入间隔为0.4cm的电穿孔小槽中。
将适量的RNA加入到细胞中，之后在冰上充分冷却5分钟。使用电穿孔仪(Bio-Rad)，以960uF、250V施加脉冲。立即再悬浮于8mL培养基中，将一部分播种在皿中。培养一定时间后，以1mg/mL的浓度向培养皿中添加G418(新霉素)。之后，每间隔4天交换培养液一次继续培养。自播种时起培养约20天后，从培养皿中克隆存活细胞的集落，继续培养。通过克隆上述集落，可以建立pRepTPF1复制子RNA自主复制的细胞。至于复制子RNA是否进行复制，这要通过定量RT-PCR法分析细胞性RNA中所含的复制复制子RNA的拷贝数来确定。
负链的定量方法
复制子RNA发生自主复制，这要根据细胞中是否可以检测到HCV RNA的5’UTR区的负链来研究。负链的特异性定量法按照与日本特愿平08-187097号公报中记载的负链RNA的特异性检测法相同的方法来进行。
将以pRepTPF-1为模板、在体外合成的RNA通过电穿孔导入到细胞中，由该细胞可以检测出显著量的负链，确认到在细胞内复制子RNA进行了自主复制。
《实施例3：适应突变的分析》
按照实施例2，将以pRepTPF1为模板、在体外合成的RNA转染到Huh7细胞中，由此建立复制子RNA复制细胞株。使用ISOGEN(日本ジ一ン)，按照生产商推荐的条件，从上述复制细胞株中提取细胞内RNA。
按照与实施例1中由TPF1获得基因的步骤相同的步骤，由上述细胞内RNA扩增几乎遍及复制子RNA的全区的DNA。具体而言，以提取的细胞内RNA为模板，利用SuperSucript II逆转录酶(Invitrogen)和XR58R引物，合成与复制子RNA相符的cDNA。
使用上述cDNA中的一部分，在EMCV-S1引物：5’-tgcacatgctctacatgtgt ttagtcgagg-3’(SEQ ID NO：60)和HC9405R引物的存在下，使用Takara LA Taq DNA聚合酶(宝酒造)，进行聚合酶链反应(PCR)(以94℃、20秒、68℃、6分钟为一次热循环反应，重复进行30次热循环反应)，从而进行HCV cDNA的扩增。确定克隆到pGEM-T easy载体中的克隆的序列时，确认碱基数第5752位的A置换成T、第6237位的G置换成A。其结果，相当于SEQ ID NO：2的氨基酸序号1804的氨基酸由Q(谷氨酰胺)突变为L(亮氨酸)、相当于氨基酸序号1966的氨基酸由E(谷氨酸)突变为K(赖氨酸)。
接下来，就上述氨基酸置换对复制子RNA的复制造成的影响进行研究。首先，使用Quick Mutagenesis试剂盒(Stratagene)，按照生产商推荐的方法，将氨基酸序号1804(Q→L)和氨基酸序号1906(E→K)的适应突变导入实施例2中制作的HCV RNA复制子pRepTPF1中。将导入了该氨基酸置换的复制子RNA命名为pRep4B。
将不具有引起突变的核苷酸序列的pRepTPF1和具有氨基酸突变的pRep4B的质粒DNA用XbaI切断，以所得产物为模板，使用Megascript T7试剂盒(Ambion)来合成RNA。按照生产商推荐的方法纯化RNA。将纯化的各RNA转染到Huh7细胞中，在G418的存在下培养约20天，用结晶紫对存活细胞进行了染色。计测被染色的集落数，计算转染的每1μg复制子RNA量的集落数。
转染1μgRepTPF1RNA时，选择1个G418耐性集落，而转染1μgRep4B RNA时，选择104个集落。即，认为引起复制子RNA中的氨基酸突变的碱基突变在Huh7细胞中是提高复制子RNA的复制效率的适应突变。
《实施例4：适应突变对HCV RNA复制的效果》
将实施例2中制作的完全长HCV DNA pTPF1用限制酶SfiI切断，在其切断部位连接插入将pRep4B用限制酶SfiI切断的片段，从而制作插入有适应突变的完全长HCV DNA pTPF1/4B。
将由插入有该适应突变的pTPF1/4B合成的完全长HCV RNA在Huh7细胞中的复制效率与pTPF1的情形进行比较。具体而言，利用与实施例2相同的方法在体外合成完全长HCV RNA，并转染到Huh7细胞中。将进行了转染的细胞立即再悬浮于10mL培养基中，以每孔1mL的量向12孔平板的各孔(直径为22.1mm)中播种，开始培养。于4小时、24小时、48小时和72小时回收培养上清。将回收的培养上清以2krpm的转速离心10分钟，回收上清。使用HCV核心抗原试剂盒(富士レビオ、ルミパルス)测定100μL的上清。
如图1所示，在导入有适应突变的pTPF1/4B的上清中，核心抗原的测定值在每一点均高于不具有适应突变的对照pTPF1的情形。这表明：通过将本发明的适应突变导入到完全长HCV RNA复制子中，HCV RNA复制子在细胞内高效率地进行复制，并将核心蛋白分泌到上清中。这显示出与在肝脏中复制的结构相同的全长型基因组可以在体外进行复制。
特别是在本发明的TPF1-NS4B多肽中，认为通过将编码具有上述适应突变的TPF1-突变NS4B多肽的多核苷酸用于复制子RNA，RNA的复制效率得以提高。
《实施例5：可以再感染的HCV颗粒的建立》
在实施例4中，分泌在培养上清中的核心抗原形成病毒颗粒，研究该病毒颗粒在体外能否再感染。具体而言，将由pTPF1/FL4B合成的完全长HCV RNA转染到Huh7细胞中，培养72小时后回收培养上清。将回收的培养上清以2krpm的转速离心10分钟，之后进行滤器过滤(0.45μm、Millipore)，除去破碎的细胞等。
使进行了滤器过滤的上清与在12孔平板(直径为22.1μm)中培养的Huh7细胞在4℃的低温条件下反应3小时。反应后添加5％二氧化碳，移入37℃的培养器内进行培养。于4小时、24小时、48小时、72小时和96小时用1mM EDTA-PBS剥离细胞，通过离心分离进行回收。将沉淀细胞溶解于50μL RIPA缓冲液(20mM Tris-HCl(pH7.5)，150mM NaCl，1mM EDTA，1％NP40，0.1％脱氧胆酸盐，0.1％SDScomplete protease inhibitor cocktail(蛋白酶抑制剂)(Roche diagnosticscorporation))中，通过以10krpm的转速离心5分钟来回收上清。使用HCV核心抗原试剂盒(富士レビオ、ルミパルス)测定5μL的上清。
如图2所示，在经pTPF1/4B的培养上清处理的细胞内核心抗原在4小时～24小时曾经一度减少，之后从48小时起开始上升，96小时后仍在增加。这表明：在本发明的完全长HCV RNA在细胞中复制而释放的培养上清中，含有新型的可感染Huh7细胞的病毒颗粒。
《实施例6：由干扰素感受性急性肝炎患者获得丙型肝炎病毒全长基因》
尝试着从用干扰素治疗见效的急性肝炎患者的血清中获得丙型肝炎病毒全长基因。使用RNA提取试剂ISOGEN-LS(日本ジ一ン)，按照附录说明书从患者血清中提取RNA。
利用与实施例1中由TPF1获得全长基因的方法相同的方法，从上述RNA中获得第85位～第9302位的HCV基因。将其克隆到pGEM-T easy载体中，在确定其序列时，发现该基因是属于基因型1b的典型的全长基因。
接着，确定3’非翻译区的核酸序列。向提取的2.5μL RNA中加入5pmole(0.5μL)引物8913F，在70℃下保持3分钟，之后在冰中骤冷。向其中加入2μL 5x First-Strand Buffer、1μL 0.1M的DTT、0.5μL20mM的dNTP、20单位RNase Inhibitor(宝酒造)、0.5μL SuperSucriptII逆转录酶(Invitrogen)，再加入经焦碳酸二乙酯处理过的灭菌水，使总量达到10μL。使该混合液在42℃下反应60分钟。为了破坏RNA，加入12U RNaseH(宝酒造、60U/μL)，在37℃下保持30分钟，之后在72℃下失活3分钟，用作cDNA。
使用引物8913F和RP2，按照与上述相同的方法对2μL的该cDNA进行PCR。使用一部分该PCR产物，利用8939F和R1的引物进行第二次PCR，得到约600碱基的PCR产物。将该PCR产物克隆到pGEM-T Easy载体中，确定其序列。
一方的HCV cDNA的5’末端如下分离，并确定其序列。使用HCLongH1、HC705R和Takara EX Taq DNA聚合酶(宝酒造)，对上述的一部分经RNaseH处理过的cDNA反应液进行PCR(以94℃、20秒、55℃、30秒、72℃、1分钟为一次热循环反应，重复进行35次热循环反应)，从而使已经报道的相当于HCV cDNA的第1位～709位的片段扩增。将该PCR产物克隆到pGEM-T easy载体中，确定其序列。
通过以上操作获得全病毒基因组序列，将其命名为AHC1株。所得AHC1株的全长为9594碱基长，所确定的全病毒基因组的核苷酸序列在其342位～9374位之间具有编码一长3010个氨基酸的翻译区。其核苷酸序列见SEQ ID NO：10、氨基酸序列见SEQ ID NO：11。
以下显示用于克隆和基因解析的引物。
XR58R(SEQ ID NO：12)：5’-tcatgcggct cacggacctt tcacagctag-3’
HClongA1(SEQ ID NO：13)：5’-atcgtcttca cgcagaaagc gtctagccat-3’
1b9405R(SEQ ID NO：14)：5′-gcctattggc ctggagtgtt tagctc-3’
HC85F(SEQ ID NO：15)：5′-atggcgttag tatgagtgtc gtgcagcct-3’
HC9302R(SEQ ID NO：16)：5’-tcgggcacga gacaggctgt gatatatgtc t-3’
HC8913F(SEQ ID NO：47)：5’-cttgaaaaag ccctggattg tcagat-3’
HC8939F(SEQ ID NO：46)：5’-ctacggggcc tgttactcca ttgaac-3’
R1(SEQ ID NO：48)：5’-acatgatctg cagagaggcc agtatcagca ctctc-3
HClongH1(SEQ ID NO：49)：5′-gccagccccc tgatgggggc gacactccac c-3’
HC705R(SEQ ID NO：50)：5′-agccgcatgt aagggtatcg atgac-3”
RP2(SEQ ID NO：51)：5’-acatgatctg cagagaggcc-3’
M13PrimerM3(SEQ ID NO：24)：5’-gtaaaacgac ggccagt-3’
M13PrimerRV(SEQ ID NO：25)：5’-caggaaacag ctatgac-3’
HC161S(SEQ ID NO：52)：5’-gagtacaccggaattgccaggacgaccggg-3’
104(SEQ ID NO：26)：5’-aggaagactt ccgagcggtc-3’
HC841S(SEQ ID NO：27)：5’-ggaacttgcc cggttgctct ttctctatct tc-3’
HC1405S(SEQ ID NO：53)：5’-attccatggt ggggaactgg gccaa-3’
E1(SEQ ID NO：28)：5’-attccatggt ggggaactgg gctaa-3’
HC2006AS(SEQ ID NO：54)：5’-catccatgtg cagccgaacc aatt-3’
HC2199AS(SEQ ID NO：55)：5’-aggggtagtg ccaaagcctg tatgggtagt-3’
HC2430S(SEQ ID NO：30)：5’-aacatcgtgg acgtgcaata cctgtacgg-3’
HC2769S(SEQ ID NO：32)：5’-ttggaccggg agatggctgc atcgtg-3’
HC3111AS(SEQ ID NO：56)：5’-ataatgaccc ccggcgactt tccgcactaa c-3’
HC3591AS(SEQ ID NO：57)：5’-catggtagac agtccagcac-3’
HC4016AS(SEQ ID NO：35)：5’-cacttggaat gtctgcggta-3’
HC4498S(SEQ ID NO：36)：5’-agggggggag gcatctcatt ttctg-3’
HC4888F(SEQ ID NO：37)：5’-tgctatgacg cgggctgtgc ttggta-3’
1b5290AS(SEQ ID NO：58)：5’-gacatgcatg tcatgatgta tttg-3’
HC5950AS(SEQ ID NO：59)：5’-ctcatgacct taaaggccac-3’
HC5858F(SEQ ID NO：40)：5’-tggcagcata ggccttggga aggt-3’
HC6315F(SEQ ID NO：41)：5’-aagacctggc tccagtccaa g-3’
5A-1(SEQ ID NO：42)：5’-ttccatgctc accgacccct c-3’
HC7090AS(SEQ ID NO：43)：5’-accttattct ctgactccac-3’
HC7743F(SEQ ID NO：44)：5’-cagaagaagg tcacctttgac-3’
HC8192S(SEQ ID NO：45)：5’-gcagcgggtc gagttcctgg tgaat-3’
《实施例7：干扰素抑制HCV RNA复制子的复制》
使用完全长HCV RNA复制子，尝试着评价干扰素对HCV复制的抑制作用。在评价干扰素的抑制作用中使用的完全长HCV RNA，使用了实施例4中可在Huh7细胞中高效率复制的pTPF1/4B和实施例6中获得的AHC1与pTPF1/4B的嵌合体。嵌合载体如下制作：将完全长HCV DNA pTPF1用限制酶AgeI和BsrGI切断，在其切断部位连接插入将AHC1用限制酶AgeI和BsrGI切断的片段，从而制作插入有AHC1的结构蛋白区的HCV DNA pTPF1/AHC1_AgeBsr。
利用与实施例2相同的方法，合成pTPF1/4B和pTPF1/AHC1_AgeBsr的完全长HCV RNA，并转染到Huh7细胞中。将进行了转染的细胞立即再悬浮于15mL培养基中，以每孔1mL的量向12孔平板的各孔中(直径22.1mm)播种，开始培养。
培养开始24小时后，与溶解有各种浓度(0.1IU/mL～300IU/mL)的干扰素的培养基交换。再培养24小时后，用1mM EDTA-PBS剥离细胞，通过离心分离进行回收。将沉淀细胞溶解于50μLRIPA缓冲液(20mM Tris-HCl(pH7.5)，150mM NaCl，1mM EDTA，1％NP40，0.1％脱氧胆酸盐，0.1％SDS complete protease inhibitor cocktail(Rochediagnostics corporation))中，通过以10krpm的转速离心5分钟来回收上清。使用HCV核心抗原试剂盒(富士レビオ、ルミパルス)测定5μL的上清。
通过曲线算出细胞内的抗原量相对于对照(干扰素未添加区)显示出50％的核心抗原量的干扰素浓度，作为IC50。结果见表2。
[表2]
| RNA | HCV RNA复制子复制抑制活性：IC50(IU/m) |
| pTPF1/4B | ＞300 |
| pTPF1/AHC1_AgeBsr | 33 |
上述试验结果显示：pTPF1/4B为干扰素抵抗性，而一方的pTPF1/AHC1_AgeBsr为干扰素感受性。由此认为：本发明的完全长HCV RNA复制子是干扰素抵抗性的RNA复制子，对开发显示出干扰素抵抗性的丙型肝炎病毒的治疗药有用。
《实施例8：环孢菌素A抑制HCV RNA复制子的复制》
尝试着评价环孢菌素A对HCV RNA复制子复制的抑制作用。评价中使用了pTPF1/4B。利用与实施例2相同的方法，对Huh7细胞进行转染，播种在12孔平板中。培养4小时后，交换为溶解有1μg环孢菌素A的培养基。
交换为含有环孢菌素A的培养基后，对于培养24小时、48小时和72小时后的细胞，利用与实施例7相同的方法，使用HCV核心抗原试剂盒(富士レビオ、ルミパルス)测定细胞内的HCV核心抗原量。
如图3所示，确认到环孢菌素A(CsA)添加区在转染后4小时达到最大值，之后减少。而对照(CsA未添加区)在4小时～24小时间曾经一度减少，之后从48小时起开始上升，72小时后仍在增加。由此确认了CsA具有抗丙型肝炎病毒活性。这表明：本发明的完全长HCVRNA可以用作迄今为止报道的丙型肝炎治疗药的试验系统(筛选方法)。其还可用作用于筛选对HCV的复制和/或HCV蛋白的翻译产生影响的各种物质的试验系统。
《实施例9：TPF1株的NS4B蛋白中的适应突变的效果》
研究由使用了TPF1株的RNA复制子得到的NS4B蛋白中的两个氨基酸的适应突变对其他基因型1b的HCV基因中的复制子RNA的复制的影响。
按照向实施例6中得到的AHC1株的3010个氨基酸的NS4B区蛋白中导入适应突变的方式，向核苷酸中导入突变。具体而言，使用Quick Mutagenesis试剂盒(Stratagene)，按照生产商推荐的方法导入核苷酸的突变，使第1804位的氨基酸由Q(谷氨酰胺)向L(亮氨酸)突变、使第1966位的氨基酸由E(谷氨酸)向K(赖氨酸)突变。所得克隆的RNA的核苷酸序列见SEQ ID NO：61、氨基酸序列见SEQ ID NO：62。
除了使用所得的导入有突变的适应突变AHC1株的全长多核苷酸以外，重复实施例2的操作，获得具有适应突变的质粒DNApRepAHC1/4B。以将该pRepAHC1/4B用限制酶XbaI切断的产物为模板，获得RepAHC1/4B复制子RNA，并转染到人肝癌细胞(Huh7、JCRB0403)中，建立RepAHC1/4B复制子RNA自主复制的细胞株。
使用未导入适应突变的AHC1株的全长多核苷酸作为对照，重复相同的操作时，可以建立复制子RNA自主复制的细胞株，但效率为RepAHC1/4B复制子的约千分之一。由此可知：通过向基因型1b的HCV基因中导入编码NS4b蛋白的2个适应突变的核苷酸的突变，复制子RNA高效率地进行自主复制。
接下来，除了使用所得细胞株以外，重复实施例3的操作，确定复制的复制子RNA的核苷酸序列。其结果，碱基数第3685位的C突变为T、对应于SEQ ID NO：11的氨基酸序号1115的氨基酸由P(脯氨酸)突变为L(亮氨酸)。将该突变导入上述pRepAHC1/4B中，得到质粒pRepAHC1/4Bm。将由pRepAHC1/4B得到的复制子RNA即RepAHC1/4B和由pRepAHC1/4Bm得到的复制子RNA即RepAHC1/4Bm转染到Huh7中，计算得到的集落数。RepAHC1/4B的核苷酸序列见SEQ ID NO：67，RepAHC1/4Bm的核苷酸序列见SEQ IDNO：68。
转染1μg的RepAHC1/4B RNA时，选择约10E3个G418耐性集落，而转染1μg的RepAHC1/4Bm RNA时，选择约10E6个集落。由此可知：除了NS4B蛋白中的上述两个适应突变外，通过导入一个以上的其他适应突变，复制子RNA的复制效率得以提高。
接下来，作为完全长HCV DNA，除了使用pAHC1代替pTPF1、以及使用pRepAHC1/4Bm代替pRep4B以外，重复实施例4的操作，制作完全长HCV DNA即pAHC1和pAHC1/4Bm，将由pAHC1制作的复制子RNA即AHC1和由pAHC1/4Bm制作的复制子RNA即AHC1/4Bm转染到Huh7细胞中，之后测定培养上清中的核心抗原量。结果见图4。
如图4所示，转染了具有适应突变的AHC1/4Bm的复制子RNA的细胞，其24小时、48小时和72小时后的培养上清中的核心抗原测定值高于对照的转染了AHC1的细胞的培养上清中的核心抗原测定值。需要说明的是，作为复制子RNA的AHC1/4Bm的核苷酸序列见SEQ ID NO：63、所编码的氨基酸序列见SEQ ID NO：64。
产业实用性
本发明的复制子RNA，通过将其导入细胞内，可以进行自主复制，产生丙型肝炎病毒基因、丙型肝炎病毒蛋白和感染性颗粒。以导入了该复制子RNA的复制子复制细胞作为丙型肝炎病毒感染的试管内模型，反映出HCV在机体内的增殖机制，可以将该复制子复制细胞用于HCV治疗药的筛选方法。并且，上述筛选方法除了用于筛选HCV治疗药以外，还可在治疗药的制造步骤中用于品质管理，可以用作药品的制造方法。
以上，虽然按照特定方式说明了本发明，但本领域技术人员自明的变形或改良也包含在本发明的范围内。
序列表
<110>株式会社先端生命科学研究所
<120>HCV基因
<130>ALS-805
<150>JP2007-119667
<151>2007-04-27
<160>68
<170>PatentIn version 3.1
<210>1
<211>9594
<212>RNA
<213>丙型肝炎病毒
<400>1
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ccccccuccc gggagagcca uaguggucug cggaaccggu gaguacaccg gaauugccag 180
gacgaccggg uccuuucuug gaucaacccg cucaaugccu ggagauuugg gcgugccccc 240
gcgagacugc uagccgagua guguuggguc gcgaaaggcc uugugguacu gccugauagg 300
gugcuugcga gugccccggg aggucucgua gaccgugcau caugagcaca aauccuaaac 360
cucaaagaaa aaccaaacgu aacaccaacc gccgcccaca ggacgucaag uucccgggcg 420
guggccagau cguuggugga guuuaccugu ugccgcgcag gggccccagg uugggugugc 480
gcgcgacuag gaagacuucc gagcggucgc aaccucgugg aaggcgacaa ccuaucccca 540
aggcucgcca gcccgagggc agggccuggg cucagcccgg guauccuugg ccccucuaug 600
gcaacgaggg ucuggggugg gcaggauggc uccugucacc ccguggcucu cggccuaguu 660
ggggccccac ggacccccgg cguaggucgc guaauuuggg uaaggucauc gauacccuca 720
caugcggcuu cgccgaccuc augggguaca uuccgcucgu cggcgccccc cuaggaggcg 780
cugccagggc ccuggcgcau ggcguccggg uucuggagga cggcgugaac uaugcaacag 840
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ucccagcuuc cgcucacgaa gugcgcaacg uauccgggcu guaccauguc acgaacgacu 960
gcuccaacuc aagcauugug uaugaggcag cggacaugau caugcacacc cccgggugcg 1020
ugcccugcgu ccgggagggu aacuccuccc gcugcugggu agcgcucacu cccacgcucg 1080
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ggcacuacgc accucaaccg ugugguauug uacccgcguu gcagguaugu gguccagugu 1860
auugcuucac cccaagcccc gucguggugg ggacgaccga ucgcuucggc gcccccacgu 1920
acaacugggg ggagaaugag acggacgugc uacuccucaa caauacgcgg ccgccgcacg 1980
gcaacugguu cggcuguaca uggaugaaua guaccggguu caccaagacg ugugggggcc 2040
cccccugcaa caucgggggg uuuggcaaca acaccuugac cugcccuacg gauugcuucc 2100
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ucaaggucag gauguaugug gggggugugg agcacaggcu caccgccgcg ugcaauugga 2280
cucggggaga gcgcugcaac uuggaggaua gggacagauc ggagcucagc ccgcugcuac 2340
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cugguuugau ccaccuccac cagaacaucg uggacgugca auaccuguac gguguggggu 2460
caucgguugu cuccauugca aucagguggg aguaugucgu gcugcucuuc cuccuccugg 2520
cggacgcgcg yguuugcgcc ugcuugugga ugaugcugcu gauagcccaa gcugaggccg 2580
ccuuagagaa ccuggugauc cucaaugcgg cgucuguggc cggagcgcau ggcguucucu 2640
cuuuccuugu guucuucugc gcugccuggu acaucaaggg caagcugguc cccggggcgg 2700
cauaugccuu cuauggugua uggccgcugc uccugcuucu gcugucauua ccaccacgag 2760
cauacgccuu ggaccgggag auggcugcau cgugcggagg cgcgguuuuc guaggucuga 2820
ugcuccugac cuugucacca cacuacaagg uguuucucgc uaggcucaua uggugguuac 2880
aguauuuuau caccagggcc gaggcgcacu ugcaggugug gguccccccc cucaacguuc 2940
gggggggccg cgaugccauc auccuccuca cguguguggu ccacccagag cuaauuuuug 3000
acaucaccaa aaucuugcuc gccaugcucg guccgcucau ggugcuccag gcuggccuaa 3060
cuagagugcc guacuucgua cgcgcucaag ggcucauccg ugcaugcaug uuagugcgga 3120
aagucgcugg gggccacuau guccaaaugg cccucaugaa acuggccgca cugacgggua 3180
cguacguuua ugaccaucuu acuccgcugc aggacugggc ccacgcgggc uugcgagacc 3240
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cgaagacccu ggccggcccg aagggcccaa ucacccaaau guacaccaau guggaccaag 3660
accucgucgg cuggccggcg ccccccgggg cgcgcucccu gacaccgugc accugcggca 3720
gcucggaccu cuaccugguc acgaggcaug cugaugucau uccggugcgc cggcggggcg 3780
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gggggguugc aaaggcggug gauuuuguac cuguugaguc uauggaaacc accaugcggu 3960
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aucuacacgc ucccacuggc aguggcaaga gcacuaaggu gccggcugcg uacgcagccc 4080
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caacaagcgg agaugucguu gucguggcaa cagacgcucu aaugacgggc uucaccggcg 4680
acuuugacuc agugaucgac uguaauacuu gugucaccca gacaguugau uucagcuugg 4740
acccuaccuu caccauugag acgacaaccg ugccccaaga cgcggugucg cguucgcagc 4800
gacgaggcag gacuggcagg ggcaggaugg gcauauacag guuuguggcu ccaggggaac 4860
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gguaugagcu cacgcccgcc gagaccucag ucagguugcg ggcuuaccua aauacaccag 4980
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ggcuaggagc cguccagaau gaggucaucc ucacacaucc cauaaccaaa uacaucaugg 5280
caugcauguc ggcugaccua gaggucguca cuagcaccug ggugcugguc ggcggggucc 5340
uugcagcucu ggccgcguac ugccugacga cgggcagcgu ggucauugug ggcaggauca 5400
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aaauggaaga gugugccuca caccuccccu acaucgaaca gggaaugcag cucgccgaac 5520
aauucaagca gaaggcgcuc ggguugcugc agacagccac caagcaagcg gaagccgcug 5580
cuccuguggu ggaguccaag uggcgagccc uugaggccuu cugggcgaag cacaugugga 5640
auuucaucag cgggauacag uacuuagcag gcuuguccac ucugccuggg aaccccgcga 5700
uagcaucacu gauggcauuc acagccucua ucaccagccc gcuuaccacc caacacaccc 5760
uccuguuuaa caucuuggga ggaugggugg ccgcccaacu ugcccccccc ggugcugccu 5820
cggcuuucgu gggcgccggc auugcuggcg cagcuguugg cagcauaggc cuugggaagg 5880
ugcuugugga cauccuggcg gguuauggag cagggguggc aggcgcgcuc guggccuuca 5940
aggucaugag cggcgagaug cccuccaccg aggaccuggu caacuuacuc ccugccaucc 6000
ucucuccugg ugcccuuguc gucggggucg ugugcgcagc aauacugcgu cggcaugugg 6060
gcccggggga gggggcugug caauggauga accggcugau agcguucgcc ucgcggggua 6120
accacgucuc ccccacgcac uaugugccug agagcgacgc ugcagcgcgu gucacacaga 6180
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acugcuccac accaugcucc ggcucguggc uuagggacgu uugggacugg auaugcacgg 6300
uuuugaguga cuucaagacc uggcuccagu ccaagcuccu gccacgguua ccgggaguuc 6360
cauuccuuuc augccaacgu ggguauaagg gggucuggcg gggagauggc aucaugcaga 6420
ccuccugccc auguggagca caaaucgccg gacaugucaa gaacgguucc augaggaucg 6480
uugggccuaa aaccuguagc aacacguggc acggaacauu ccccauuaac gcgcacacca 6540
cgggccccug cacacccucc ccagcgccga acuacucuaa ggcguugugg cggguggcug 6600
cugaggagua cguggaaguc acgcgggugg gggauuucca uuacgugacg ggcaugacca 6660
cugacaacgu aaaaugccca ugccagguuc cggcccccga guucuucaca gagguggaug 6720
ggguacggcu gcacagguac gcuccggcgu gcaaaccucu ccuacgggau gaggucacau 6780
uccaggucgg gcucaaccag uucccgguug ggucacagcu cccaugcgag cccgaaccgg 6840
auguaucagu gcucacuucc augcuuaccg acccuuccca caucacagca gagacggcua 6900
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ggcagaaaaa ggucaccuuu gacagacugc aaguccugga cgaccauuac cgggacgugc 7800
ucaaggagau gaaggcgaag gcguccacag uuaaggcuaa acuucuaucc guagaagagg 7860
ccugcaagcu gacgccccca cacucagcca gguccaaauu uggcuauggg gcgaaggacg 7920
uccggaaccu auccagcaag gccguuaacc acaucaacuc cguguggaag gacuugcugg 7980
aagacacuga gacaccaauu gacaccacca ucauggcaaa aaaugagguc uucuguguuc 8040
aaccagagaa gggaggccgc aagccagcuc gccuuaucgu auacccagac uugggggugc 8100
gugugugcga gaaaauggcc cuuuacgacg uggucuccac ucuuccucag gccgugaugg 8160
gcuccucaua cggauuccag uacucuccug ggcagcgggu cgaguuccug gugaaugccu 8220
ggaaaucaaa gaagaacccu augggcuucg cauaugacac ccgcuguuuu gacucaacgg 8280
ucaccgagaa cgacauccgu guugaggagu caauuuacca auguugugac uuggcccccg 8340
aggccagaca ggugauaagg ucgcucacag agcggcuuua ugucgggggc ccccugacua 8400
auucaaaagg gcagaacugc gguuaucgcc ggugccgcgc cagcggcgug cugacgacua 8460
gcugcgguaa uacccucaca uguuacuuga aggccucugc agccugucga gcugcaaagc 8520
uccaggacug cacgaugcuc gugugcgggg acgaccuugu cguuaucugu gaaagcgcgg 8580
ggacccagga ggacgcggcg agccuacgag ucuucacgga ggcuaugacu agguacuccg 8640
ccccccccgg ggacccgccc cgaccggaau acgacuugga guugauaaca ucaugcuccu 8700
ccaacguguc ggucgcgcac gaugcaucug gcaaacgggu guauuaccuc acccgugacc 8760
ccaccacccc ccuugcgcgg gcugcguggg agacagcuaa acacacucca gucaacuccu 8820
ggcuaggcaa caucaucaug uaugcgccca cccucugggc aaggaugauu cugaugacuc 8880
acuucuucuc cauccuucua gcucaggagc agcuugaaaa agcccuggau ugucagaucu 8940
acggggccac uuacuccauu gaaccacuug accuaccuca gaucauucaa cgacuccaug 9000
gucuuagcgc auucucacuc cauaguuacu cuccagguga aaucaauagg guggcuucau 9060
gccucaggaa acuuggggua ccgcccuugc gagucuggag acaucgggcc agaagugucc 9120
gcgcuaagcu acugucccag ggggggaggg cugccacuug uggcaaguac cucuucaacu 9180
gggcaguaag gaccaagcuc aaacucacuc caaucccggc ugcgucccag uuggacuugu 9240
ccggcugguu cauugcuggu uacagcgggg gagacauaua ucacagccug ucucgugccc 9300
gaccccgcug guuuauguug ugccuacucc uacuuucugu ggggguaggc aucuaccugc 9360
uccccaaucg augaacgggg ggcuaaacac uccaggccaa uaggccauuc uguuuuuuuu 9420
uuuuuuuuuu uuuuuuuuuu uuuuuuuuuu uuuuuuuuuu uuuuuuccuu uuuuuuuuuu 9480
uuuuucccuu ucuuuuggug gcuccaucuu agcccuaguc acggcuagcu gugaaagguc 9540
cgugagccgc augacugcag agagugcuga uacuggccuc ucugcagauc augu 9594
<210>2
<211>3010
<212>PRT
<213>丙型肝炎病毒
<400>2
Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Thr Lys Arg Asn Thr Asn
1 5 10 15
Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gly Gly Gln Ile Val Gly
20 25 30
Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Arg Leu Gly Val Arg Ala
35 40 45
Thr Arg Lys Thr Ser Glu Arg Ser Gln Pro Arg Gly Arg Arg Gln Pro
50 55 60
Ile Pro Lys Ala Arg Gln Pro Glu Gly Arg Ala Trp Ala Gln Pro Gly
65 70 75 80
Tyr Pro Trp Pro Leu Tyr Gly Asn Glu Gly Leu Gly Trp Ala Gly Trp
85 90 95
Leu Leu Ser Pro Arg Gly Ser Arg Pro Ser Trp Gly Pro Thr Asp Pro
100 105 110
Arg Arg Arg Ser Arg Asn Leu Gly Lys Val Ile Asp Thr Leu Thr Cys
115 120 125
Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Leu Val Gly Ala Pro Leu
130 135 140
Gly Gly Ala Ala Arg Ala Leu Ala His Gly Val Arg Val Leu Glu Asp
145 150 155 160
Gly Val Asn Tyr Ala Thr Gly Asn Leu Pro Gly Cys Pro Phe Ser Ile
165 170 175
Phe Leu Leu Ala Leu Leu Ser Cys Leu Thr Ile Pro Ala Ser Ala His
180 185 190
Glu Val Arg Asn Val Ser Gly Leu Tyr His Val Thr Asn Asp Cys Ser
195 200 205
Asn Ser Ser Ile Val Tyr Glu Ala Ala Asp Met Ile Met His Thr Pro
210 215 220
Gly Cys Val Pro Cys Val Arg Glu Gly Asn Ser Ser Arg Cys Trp Val
225 230 235 240
Ala Leu Thr Pro Thr Leu Ala Ala Arg Asn Ser Ser Val Pro Thr Ala
245 250 255
Thr Ile Arg Arg His Val Asp Leu Leu Val Gly Ala Ala Ala Phe Cys
260 265 270
Ser Ala Met Tyr Val Gly Asp Leu Cys Gly Ser Val Phe Leu Val Ser
275 280 285
Gln Leu Phe Thr Phe Ser Pro Arg Arg Tyr Glu Thr Val Gln Asp Cys
290 295 300
Asn Cys Ser Leu Tyr Pro Gly His Val Ser Gly His Arg Met Ala Trp
305 310 315 320
Asp Met Met Met Asn Trp Ser Pro Thr Thr Ala Leu Val Val Ser Gln
325 330 335
Leu Leu Arg Ile Pro Gln Ala Val Val Asp Met Val Val Gly Ala His
340 345 350
Trp Gly Val Leu Ala Gly Leu Ala Tyr Tyr Ser Met Val Gly Asn Trp
355 360 365
Ala Lys Val Leu Ile Val Met Leu Leu Phe Ala Gly Val Asp Gly Lys
370 375 380
Thr Tyr Val Thr Gly Gly Ala Gln Ser Arg Ala Thr Gln Gly Phe Ala
385 390 395 400
Ser Leu Phe Thr Arg Gly Pro Ser Gln Lys Leu Gln Leu Val Asn Ser
405 410 415
Asn Gly Ser Trp His Ile Asn Arg Thr Ala Leu Asn Cys Asn Asp Ser
420 425 430
Phe Gln Thr Gly Phe Leu Ala Ala Leu Phe Tyr Ala His Arg Phe Asn
435 440 445
Ser Ser Gly Cys Pro Glu Arg Met Ala Ser Cys Arg Pro Ile Asp Thr
450 455 460
Phe Asp Gln Gly Trp Gly Pro Ile Thr His Val Ala Arg Arg Thr Ser
465 470 475 480
Asp Gln Arg Pro Tyr Cys Trp His Tyr Ala Pro Gln Pro Cys Gly Ile
485 490 495
Val Pro Ala Leu Gln Val Cys Gly Pro Val Tyr Cys Phe Thr Pro Ser
500 505 510
Pro Val Val Val Gly Thr Thr Asp Arg Phe Gly Ala Pro Thr Tyr Asn
515 520 525
Trp Gly Glu Asn Glu Thr Asp Val Leu Leu Leu Asn Asn Thr Arg Pro
530 535 540
Pro His Gly Asn Trp Phe Gly Cys Thr Trp Met Asn Ser Thr Gly Phe
545 550 555 560
Thr Lys Thr Cys Gly Gly Pro Pro Cys Asn Ile Gly Gly Phe Gly Asn
565 570 575
Asn Thr Leu Thr Cys Pro Thr Asp Cys Phe Arg Lys His Pro Glu Ala
580 585 590
Thr Tyr Thr Lys Cys Gly Ser Gly Pro Trp Leu Thr Pro Arg Cys Met
595 600 605
Val Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe
610 615 620
Ser Ile Phe Lys Val Arg Met Tyr Val Gly Gly Val Glu His Arg Leu
625 630 635 640
Thr Ala Ala Cys Asn Trp Thr Arg Gly Glu Arg Cys Asn Leu Glu Asp
645 650 655
Arg Asp Arg Ser Glu Leu Ser Pro Leu Leu Leu Ser Thr Thr Glu Trp
660 665 670
Gln Val Leu Pro Cys Ser Phe Thr Thr Leu Pro Ala Leu Ser Thr Gly
675 680 685
Leu Ile His Leu His Gln Asn Ile Val Asp Val Gln Tyr Leu Tyr Gly
690 695 700
Val Gly Ser Ser Val Val Ser Ile Ala Ile Arg Trp Glu Tyr Val Val
705 710 715 720
Leu Leu Phe Leu Leu Leu Ala Asp Ala Arg Val Cys Ala Cys Leu Trp
725 730 735
Met Met Leu Leu Ile Ala Gln Ala Glu Ala Ala Leu Glu Asn Leu Val
740 745 750
Ile Leu Asn Ala Ala Ser Val Ala Gly Ala His Gly Val Leu Ser Phe
755 760 765
Leu Val Phe Phe Cys Ala Ala Trp Tyr Ile Lys Gly Lys Leu Val Pro
770 775 780
Gly Ala Ala Tyr Ala Phe Tyr Gly Val Trp Pro Leu Leu Leu Leu Leu
785 790 795 800
Leu Ser Leu Pro Pro Arg Ala Tyr Ala Leu Asp Arg Glu Met Ala Ala
805 810 815
Ser Cys Gly Gly Ala Val Phe Val Gly Leu Met Leu Leu Thr Leu Ser
820 825 830
Pro His Tyr Lys Val Phe Leu Ala Arg Leu Ile Trp Trp Leu Gln Tyr
835 840 845
Phe Ile Thr Arg Ala Glu Ala His Leu Gln Val Trp Val Pro Pro Leu
850 855 860
Asn Val Arg Gly Gly Arg Asp Ala Ile Ile Leu Leu Thr Cys Val Val
865 870 875 880
His Pro Glu Leu Ile Phe Asp Ile Thr Lys Ile Leu Leu Ala Met Leu
885 890 895
Gly Pro Leu Met Val Leu Gln Ala Gly Leu Thr Arg Val Pro Tyr Phe
900 905 910
Val Arg Ala Gln Gly Leu Ile Arg Ala Cys Met Leu Val Arg Lys Val
915 920 925
Ala Gly Gly His Tyr Val Gln Met Ala Leu Met Lys Leu Ala Ala Leu
930 935 940
Thr Gly Thr Tyr Val Tyr Asp His Leu Thr Pro Leu Gln Asp Trp Ala
945 950 955 960
His Ala Gly Leu Arg Asp Leu Ala Val Ala Val Glu Pro Val Val Phe
965 970 975
Ser Asp Met Glu Thr Lys Val Ile Thr Trp Gly Ala Asp Thr Ala Ala
980 985 990
Cys Gly Asp Ile Ile Ser Gly Leu Pro Val Ser Ala Arg Arg Gly Arg
995 1000 1005
Glu Ile Leu Leu Gly Pro Ala Asp Arg Phe Gly Glu Gln Gly Trp
1010 1015 1020
Arg Leu Leu Ala Pro Ile Thr Ala Tyr Ala Gln Gln Thr Arg Gly
1025 1030 1035
Leu Leu Gly Cys Ile Ile Thr Ser Leu Thr Gly Arg Asp Lys Asn
1040 1045 1050
Gln Val Glu Gly Glu Val Gln Val Val Ser Thr Ala Thr Gln Ser
1055 1060 1065
Phe Leu Ala Thr Cys Val Asn Gly Val Cys Trp Thr Val Tyr His
1070 1075 1080
Gly Ala Gly Ser Lys Thr Leu Ala Gly Pro Lys Gly Pro Ile Thr
1085 1090 1095
Gln Met Tyr Thr Asn Val Asp Gln Asp Leu Val Gly Trp Pro Ala
1100 1105 1110
Pro Pro Gly Ala Arg Ser Leu Thr Pro Cys Thr Cys Gly Ser Ser
1115 1120 1125
Asp Leu Tyr Leu Val Thr Arg His Ala Asp Val Ile Pro Val Arg
1130 1135 1140
Arg Arg Gly Asp Ser Arg Gly Ser Leu Leu Ser Pro Arg Pro Ile
1145 1150 1155
Ser Tyr Leu Lys Gly Ser Ser Gly Gly Pro Leu Leu Cys Pro Leu
1160 1165 1170
Gly His Ala Val Gly Ile Phe Arg Ala Ala Val Cys Thr Arg Gly
1175 1180 1185
Val Ala Lys Ala Val Asp Phe Val Pro Val Glu Ser Met Glu Thr
1190 1195 1200
Thr Met Arg Ser Pro Val Phe Thr Asp Asn Ser Ser Pro Pro Ala
1205 1210 1215
Val Pro Gln Thr Phe Gln Val Ala His Leu His Ala Pro Thr Gly
1220 1225 1230
Ser Gly Lys Ser Thr Lys Val Pro Ala Ala Tyr Ala Ala Gln Gly
1235 1240 1245
Tyr Lys Val Leu Val Leu Asn Pro Ser Val Ala Ala Thr Leu Gly
1250 1255 1260
Phe Gly Ala Tyr Met Ser Lys Ala His Gly Val Glu Pro Asn Ile
1265 1270 1275
Arg Thr Gly Val Arg Thr Ile Thr Thr Gly Ala Ser Ile Thr Tyr
1280 1285 1290
Ser Thr Tyr Gly Lys Phe Leu Ala Asp Gly Gly Cys Ser Gly Gly
1295 1300 1305
Ala Tyr Asp Ile Ile Ile Cys Asp Glu Cys His Ser Thr Asp Ser
1310 1315 1320
Thr Ser Ile Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr
1325 1330 1335
Ala Gly Ala Arg Leu Val Val Leu Ala Thr Ala Thr Pro Pro Gly
1340 1345 1350
Ser Val Thr Val Pro His Pro Asn Ile Glu Glu Val Ala Leu Pro
1355 1360 1365
Ser Thr Gly Glu Ile Pro Phe Tyr Gly Lys Ala Ile Pro Ile Glu
1370 1375 1380
Thr Ile Lys Gly Gly Arg His Leu Ile Phe Cys His Ser Lys Lys
1385 1390 1395
Lys Cys Asp Glu Leu Ala Ala Lys Leu Val Gly Leu Gly Val Asn
1400 1405 1410
Ala Val Ala Tyr Tyr Arg Gly Leu Asp Val Ser Val Ile Pro Thr
1415 1420 1425
Ser Gly Asp Val Val Val Val Ala Thr Asp Ala Leu Met Thr Gly
1430 1435 1440
Phe Thr Gly Asp Phe Asp Ser Val Ile Asp Cys Asn Thr Cys Val
1445 1450 1455
Thr Gln Thr Val Asp Phe Ser Leu Asp Pro Thr Phe Thr Ile Glu
1460 1465 1470
Thr Thr Thr Val Pro Gln Asp Ala Val Ser Arg Ser Gln Arg Arg
1475 1480 1485
Gly Arg Thr Gly Arg Gly Arg Met Gly Ile Tyr Arg Phe Val Ala
1490 1495 1500
Pro Gly Glu Arg Pro Ser Gly Met Phe Asp Ser Ser Val Leu Cys
1505 1510 1515
Glu Cys Tyr Asp Ala Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala
1520 1525 1530
Glu Thr Ser Val Arg Leu Arg Ala Tyr Leu Asn Thr Pro Gly Leu
1535 1540 1545
Pro Val Cys Gln Asp His Leu Glu Phe Trp Glu Gly Val Phe Thr
1550 1555 1560
Gly Leu Thr His Ile Asp Ala His Phe Leu Ser Gln Thr Lys Gln
1565 1570 1575
Ala Gly Asp Asn Phe Pro Tyr Leu Val Ala Tyr Gln Ala Thr Val
1580 1585 1590
Cys Ala Arg Ala Gln Ala Pro Pro Pro Ser Trp Asp Gln Met Trp
1595 1600 1605
Lys Cys Leu Ile Arg Leu Lys Pro Thr Leu His Gly Pro Thr Pro
1610 1615 1620
Leu Leu Tyr Arg Leu Gly Ala Val Gln Asn Glu Val Ile Leu Thr
1625 1630 1635
His Pro Ile Thr Lys Tyr Ile Met Ala Cys Met Ser Ala Asp Leu
1640 1645 1650
Glu Val Val Thr Ser Thr Trp Val Leu Val Gly Gly Val Leu Ala
1655 1660 1665
Ala Leu Ala Ala Tyr Cys Leu Thr Thr Gly Ser Val Val Ile Val
1670 1675 1680
Gly Arg Ile Ile Leu Ser Gly Lys Pro Ala Ile Ile Pro Asp Arg
1685 1690 1695
Glu Val Leu Tyr Arg Glu Phe Asp Glu Met Glu Glu Cys Ala Ser
1700 1705 1710
His Leu Pro Tyr Ile Glu Gln Gly Met Gln Leu Ala Glu Gln Phe
1715 1720 1725
Lys Gln Lys Ala Leu Gly Leu Leu Gln Thr Ala Thr Lys Gln Ala
1730 1735 1740
Glu Ala Ala Ala Pro Val Val Glu Ser Lys Trp Arg Ala Leu Glu
1745 1750 1755
Ala Phe Trp Ala Lys His Met Trp Asn Phe Ile Ser Gly Ile Gln
1760 1765 1770
Tyr Leu Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Ile Ala
1775 1780 1785
Ser Leu Met Ala Phe Thr Ala Ser Ile Thr Ser Pro Leu Thr Thr
1790 1795 1800
Gln His Thr Leu Leu Phe Asn Ile Leu Gly Gly Trp Val Ala Ala
1805 1810 1815
Gln Leu Ala Pro Pro Gly Ala Ala Ser Ala Phe Val Gly Ala Gly
1820 1825 1830
Ile Ala Gly Ala Ala Val Gly Ser Ile Gly Leu Gly Lys Val Leu
1835 1840 1845
Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu
1850 1855 1860
Val Ala Phe Lys Val Met Ser Gly Glu Met Pro Ser Thr Glu Asp
1865 1870 1875
Leu Val Asn Leu Leu Pro Ala Ile Leu Ser Pro Gly Ala Leu Val
1880 1885 1890
Val Gly Val Val Cys Ala Ala Ile Leu Arg Arg His Val Gly Pro
1895 1900 1905
Gly Glu Gly Ala Val Gln Trp Met Asn Arg Leu Ile Ala Phe Ala
1910 1915 1920
Ser Arg Gly Asn His Val Ser Pro Thr His Tyr Val Pro Glu Ser
1925 1930 1935
Asp Ala Ala Ala Arg Val Thr Gln Ile Leu Ser Ser Leu Thr Ile
1940 1945 1950
Thr Gln Leu Leu Lys Arg Leu His Gln Trp Ile Asn Glu Asp Cys
1955 1960 1965
Ser Thr Pro Cys Ser Gly Ser Trp Leu Arg Asp Val Trp Asp Trp
1970 1975 1980
Ile Cys Thr Val Leu Ser Asp Phe Lys Thr Trp Leu Gln Ser Lys
1985 1990 1995
Leu Leu Pro Arg Leu Pro Gly Val Pro Phe Leu Ser Cys Gln Arg
2000 2005 2010
Gly Tyr Lys Gly Val Trp Arg Gly Asp Gly Ile Met Gln Thr Ser
2015 2020 2025
Cys Pro Cys Gly Ala Gln Ile Ala Gly His Val Lys Asn Gly Ser
2030 2035 2040
Met Arg Ile Val Gly Pro Lys Thr Cys Ser Asn Thr Trp His Gly
2045 2050 2055
Thr Phe Pro Ile Asn Ala His Thr Thr Gly Pro Cys Thr Pro Ser
2060 2065 2070
Pro Ala Pro Asn Tyr Ser Lys Ala Leu Trp Arg Val Ala Ala Glu
2075 2080 2085
Glu Tyr Val Glu Val Thr Arg Val Gly Asp Phe His Tyr Val Thr
2090 2095 2100
Gly Met Thr Thr Asp Asn Val Lys Cys Pro Cys Gln Val Pro Ala
2105 2110 2115
Pro Glu Phe Phe Thr Glu Val Asp Gly Val Arg Leu His Arg Tyr
2120 2125 2130
Ala Pro Ala Cys Lys Pro Leu Leu Arg Asp Glu Val Thr Phe Gln
2135 2140 2145
Val Gly Leu Asn Gln Phe Pro Val Gly Ser Gln Leu Pro Cys Glu
2150 2155 2160
Pro Glu Pro Asp Val Ser Val Leu Thr Ser Met Leu Thr Asp Pro
2165 2170 2175
Ser His Ile Thr Ala Glu Thr Ala Lys Arg Arg Leu Ala Arg Gly
2180 2185 2190
Ser Ser Pro Ser Leu Ala Ser Ser Ser Ala Ser Gln Leu Ser Ala
2195 2200 2205
Pro Ser Leu Lys Ala Thr Cys Thr Thr His His Asp Ser Pro Asp
2210 2215 2220
Ala Asp Leu Ile Glu Ala Asn Leu Leu Trp Arg Gln Glu Met Gly
2225 2230 2235
Gly Asn Ile Thr Arg Val Glu Ser Glu Asn Lys Val Val Ile Leu
2240 2245 2250
Asp Ser Phe Asp Pro Leu Arg Ala Glu Glu Asp Glu Arg Glu Val
2255 2260 2265
Ser Val Ala Ala Glu Ile Leu Arg Lys Thr Arg Lys Phe Pro Pro
2270 2275 2280
Ala Met Pro Ile Trp Ala Arg Pro Asp Tyr Asn Pro Pro Leu Leu
2285 2290 2295
Glu Thr Trp Lys Asp Pro Asp Tyr Val Pro Pro Val Val His Gly
2300 2305 2310
Cys Pro Leu Pro Pro Thr Lys Thr Pro Pro Ile Pro Pro Pro Arg
2315 2320 2325
Arg Lys Lys Thr Val Val Leu Thr Glu Ser Thr Val Ser Ser Ala
2330 2335 2340
Leu Ala Glu Leu Ala Thr Lys Thr Phe Gly Ser Ser Gly Ser Ser
2345 2350 2355
Ala Val Asp Ser Gly Thr Ala Thr Ala Pro Pro Asn Gln Leu Ser
2360 2365 2370
Asp Glu Val Asp Thr Gly Ser Asp Val Glu Ser Tyr Ser Ser Met
2375 2380 2385
Pro Pro Leu Glu Gly Glu Pro Gly Asp Pro Asp Leu Ser Asp Gly
2390 2395 2400
Ser Trp Ser Thr Val Ser Glu Glu Ala Gly Glu Asp Val Val Cys
2405 2410 2415
Cys Ser Met Ser Tyr Thr Trp Thr Gly Ala Leu Ile Thr Pro Cys
2420 2425 2430
Ala Ala Glu Glu Ser Lys Leu Pro Ile Asn Ala Leu Ser Asn Ser
2435 2440 2445
Leu Leu Arg His His Asn Met Val Tyr Ala Thr Thr Ser Arg Ser
2450 2455 2460
Ala Ser Gln Arg Gln Lys Lys Val Thr Phe Asp Arg Leu Gln Val
2465 2470 2475
Leu Asp Asp His Tyr Arg Asp Val Leu Lys Glu Met Lys Ala Lys
2480 2485 2490
Ala Ser Thr Val Lys Ala Lys Leu Leu Ser Val Glu Glu Ala Cys
2495 2500 2505
Lys Leu Thr Pro Pro His Ser Ala Arg Ser Lys Phe Gly Tyr Gly
2510 2515 2520
Ala Lys Asp Val Arg Asn Leu Ser Ser Lys Ala Val Asn His Ile
2525 2530 2535
Asn Ser Val Trp Lys Asp Leu Leu Glu Asp Thr Glu Thr Pro Ile
2540 2545 2550
Asp Thr Thr Ile Met Ala Lys Asn Glu Val Phe Cys Val Gln Pro
2555 2560 2565
Glu Lys Gly Gly Arg Lys Pro Ala Arg Leu Ile Val Tyr Pro Asp
2570 2575 2580
Leu Gly Val Arg Val Cys Glu Lys Met Ala Leu Tyr Asp Val Val
2585 2590 2595
Ser Thr Leu Pro Gln Ala Val Met Gly Ser Ser Tyr Gly Phe Gln
2600 2605 2610
Tyr Ser Pro Gly Gln Arg Val Glu Phe Leu Val Asn Ala Trp Lys
2615 2620 2625
Ser Lys Lys Asn Pro Met Gly Phe Ala Tyr Asp Thr Arg Cys Phe
2630 2635 2640
Asp Ser Thr Val Thr Glu Asn Asp Ile Arg Val Glu Glu Ser Ile
2645 2650 2655
Tyr Gln Cys Cys Asp Leu Ala Pro Glu Ala Arg Gln Val Ile Arg
2660 2665 2670
Ser Leu Thr Glu Arg Leu Tyr Val Gly Gly Pro Leu Thr Asn Ser
2675 2680 2685
Lys Gly Gln Asn Cys Gly Tyr Arg Arg Cys Arg Ala Ser Gly Val
2690 2695 2700
Leu Thr Thr Ser Cys Gly Asn Thr Leu Thr Cys Tyr Leu Lys Ala
2705 2710 2715
Ser Ala Ala Cys Arg Ala Ala Lys Leu Gln Asp Cys Thr Met Leu
2720 2725 2730
Val Cys Gly Asp Asp Leu Val Val Ile Cys Glu Ser Ala Gly Thr
2735 2740 2745
Gln Glu Asp Ala Ala Ser Leu Arg Val Phe Thr Glu Ala Met Thr
2750 2755 2760
Arg Tyr Ser Ala Pro Pro Gly Asp Pro Pro Arg Pro Glu Tyr Asp
2765 2770 2775
Leu Glu Leu Ile Thr Ser Cys Ser Ser Asn Val Ser Val Ala His
2780 2785 2790
Asp Ala Ser Gly Lys Arg Val Tyr Tyr Leu Thr Arg Asp Pro Thr
2795 2800 2805
Thr Pro Leu Ala Arg Ala Ala Trp Glu Thr Ala Lys His Thr Pro
2810 2815 2820
Val Asn Ser Trp Leu Gly Asn Ile Ile Met Tyr Ala Pro Thr Leu
2825 2830 2835
Trp Ala Arg Met Ile Leu Met Thr His Phe Phe Ser Ile Leu Leu
2840 2845 2850
Ala Gln Glu Gln Leu Glu Lys Ala Leu Asp Cys Gln Ile Tyr Gly
2855 2860 2865
Ala Thr Tyr Ser Ile Glu Pro Leu Asp Leu Pro Gln Ile Ile Gln
2870 2875 2880
Arg Leu His Gly Leu Ser Ala Phe Ser Leu His Ser Tyr Ser Pro
2885 2890 2895
Gly Glu Ile Asn Arg Val Ala Ser Cys Leu Arg Lys Leu Gly Val
2900 2905 2910
Pro Pro Leu Arg Val Trp Arg His Arg Ala Arg Ser Val Arg Ala
2915 2920 2925
Lys Leu Leu Ser Gln Gly Gly Arg Ala Ala Thr Cys Gly Lys Tyr
2930 2935 2940
Leu Phe Asn Trp Ala Val Arg Thr Lys Leu Lys Leu Thr Pro Ile
2945 2950 2955
Pro Ala Ala Ser Gln Leu Asp Leu Ser Gly Trp Phe Ile Ala Gly
2960 2965 2970
Tyr Ser Gly Gly Asp Ile Tyr His Ser Leu Ser Arg Ala Arg Pro
2975 2980 2985
Arg Trp Phe Met Leu Cys Leu Leu Leu Leu Ser Val Gly Val Gly
2990 2995 3000
Ile Tyr Leu Leu Pro Asn Arg
3005 3010
<210>3
<211>9594
<212>RNA
<213>丙型肝炎病毒
<400>3
gccagccccc ugaugggggc gacacuccac cauagaucac uccccuguga ggaacuacug 60
ucuucacgca gaaagcgucu agccauggcg uuaguaugag ugucgugcag ccuccaggac 120
ccccccuccc gggagagcca uaguggucug cggaaccggu gaguacaccg gaauugccag 180
gacgaccggg uccuuucuug gaucaacccg cucaaugccu ggagauuugg gcgugccccc 240
gcgagacugc uagccgagua guguuggguc gcgaaaggcc uugugguacu gccugauagg 300
gugcuugcga gugccccggg aggucucgua gaccgugcau caugagcaca aauccuaaac 360
cucaaagaaa aaccaaacgu aacaccaacc gccgcccaca ggacgucaag uucccgggcg 420
guggccagau cguuggugga guuuaccugu ugccgcgcag gggccccagg uugggugugc 480
gcgcgacuag gaagacuucc gagcggucgc aaccucgugg aaggcgacaa ccuaucccca 540
aggcucgcca gcccgagggc agggccuggg cucagcccgg guauccuugg ccccucuaug 600
gcaacgaggg ucuggggugg gcaggauggc uccugucacc ccguggcucu cggccuaguu 660
ggggccccac ggacccccgg cguaggucgc guaauuuggg uaaggucauc gauacccuca 720
caugcggcuu cgccgaccuc augggguaca uuccgcucgu cggcgccccc cuaggaggcg 780
cugccagggc ccuggcgcau ggcguccggg uucuggagga cggcgugaac uaugcaacag 840
ggaaucugcc cgguugcccu uucucuaucu uccucuuagc uuugcugucc uguuugacca 900
ucccagcuuc cgcucacgaa gugcgcaacg uauccgggcu guaccauguc acgaacgacu 960
gcuccaacuc aagcauugug uaugaggcag cggacaugau caugcacacc cccgggugcg 1020
ugcccugcgu ccgggagggu aacuccuccc gcugcugggu agcgcucacu cccacgcucg 1080
cggccaggaa uagcagcguc cccacugcga caauacgacg ccaugucgau uugcucgucg 1140
gggcggcugc uuucuguucc gcuauguacg ugggggaucu uugcggaucu guuuuccucg 1200
ucucccagcu guucaccuuu ucaccucgcc gguacgagac gguacaggac ugcaauugcu 1260
cacucuaucc cggccacgua ucaggccauc gcauggcuug ggauaugaug augaacuggu 1320
caccuacaac agccuuagug guaucgcagu uacuccggau cccacaagcc gucguggaua 1380
uggugguagg ggcccacugg ggaguccugg cgggccuugc cuacuauucc auggugggga 1440
acugggcuaa ggucuugauu gugaugcuac ucuuugccgg cgucgacggg aagaccuacg 1500
ugacaggggg ggcgcagagc cgagccacuc aaggcuuugc gucccucuuu acacgggggc 1560
cgucucagaa acuccagcuu guaaauucca acggcagcug gcacauuaac aggacugccu 1620
ugaacugcaa ugacuccuuc cagacugggu uccuugccgc gcuguuuuac gcacaccguu 1680
ucaacucguc cggaugccca gagcgcaugg ccagcugccg ccccaucgac acguucgauc 1740
aggggugggg ccccaucacu caugucgcgc gucgcacauc ggaccagagg ccuuauugcu 1800
ggcacuacgc accucaaccg ugugguauug uacccgcguu gcagguaugu gguccagugu 1860
auugcuucac cccaagcccc gucguggugg ggacgaccga ucgcuucggc gcccccacgu 1920
acaacugggg ggagaaugag acggacgugc uacuccucaa caauacgcgg ccgccgcacg 1980
gcaacugguu cggcuguaca uggaugaaua guaccggguu caccaagacg ugugggggcc 2040
cccccugcaa caucgggggg uuuggcaaca acaccuugac cugcccuacg gauugcuucc 2100
ggaagcaccc cgaggccacu uacaccaaau gcggcucggg gcccugguug acgccuaggu 2160
gcaugguuga uuacccauac agacuuuggc acuaccccug cacuguuaac uuuuccaucu 2220
ucaaggucag gauguaugug gggggugugg agcacaggcu caccgccgcg ugcaauugga 2280
cucggggaga gcgcugcaac uuggaggaua gggacagauc ggagcucagc ccgcugcuac 2340
ugucuaccac agaguggcag guacugcccu guucuuucac caccuuaccg gcccugucca 2400
cugguuugau ccaccuccac cagaacaucg uggacgugca auaccuguac gguguggggu 2460
caucgguugu cuccauugca aucagguggg aguaugucgu gcugcucuuc cuccuccugg 2520
cggacgcgcg yguuugcgcc ugcuugugga ugaugcugcu gauagcccaa gcugaggccg 2580
ccuuagagaa ccuggugauc cucaaugcgg cgucuguggc cggagcgcau ggcguucucu 2640
cuuuccuugu guucuucugc gcugccuggu acaucaaggg caagcugguc cccggggcgg 2700
cauaugccuu cuauggugua uggccgcugc uccugcuucu gcugucauua ccaccacgag 2760
cauacgccuu ggaccgggag auggcugcau cgugcggagg cgcgguuuuc guaggucuga 2820
ugcuccugac cuugucacca cacuacaagg uguuucucgc uaggcucaua uggugguuac 2880
aguauuuuau caccagggcc gaggcgcacu ugcaggugug gguccccccc cucaacguuc 2940
gggggggccg cgaugccauc auccuccuca cguguguggu ccacccagag cuaauuuuug 3000
acaucaccaa aaucuugcuc gccaugcucg guccgcucau ggugcuccag gcuggccuaa 3060
cuagagugcc guacuucgua cgcgcucaag ggcucauccg ugcaugcaug uuagugcgga 3120
aagucgcugg gggccacuau guccaaaugg cccucaugaa acuggccgca cugacgggua 3180
cguacguuua ugaccaucuu acuccgcugc aggacugggc ccacgcgggc uugcgagacc 3240
uugcaguggc aguugagccc gucgucuucu cugacaugga gacuaagguc aucaccuggg 3300
gggcagacac cgcagcgugu ggggacauca ucucgggccu acccgucucc gcccgaaggg 3360
ggagggagau acuucugggc cccgccgaca gguuuggaga gcaggggugg cgacuccucg 3420
cgccuaucac ggcuuacgcu caacagacgc ggggccuacu uggcuguauc aucaccagcc 3480
ucacaggccg ggacaagaac caggucgagg gggagguuca ggugguuucc accgcaacgc 3540
aaucuuuccu ggcgaccugc gucaacggcg uguguuggac ugucuaccau ggugccggcu 3600
cgaagacccu ggccggcccg aagggcccaa ucacccaaau guacaccaau guggaccaag 3660
accucgucgg cuggccggcg ccccccgggg cgcgcucccu gacaccgugc accugcggca 3720
gcucggaccu cuaccugguc acgaggcaug cugaugucau uccggugcgc cggcggggcg 3780
acagcagggg gagucuacuc ucucccaggc ccaucuccua cuuaaagggc uccucaggug 3840
guccacugcu uugcccccug gggcacgcug ugggcaucuu ccgggccgcu gugugcaccc 3900
gggggguugc aaaggcggug gauuuuguac cuguugaguc uauggaaacc accaugcggu 3960
cuccggucuu uacggauaau ucaucucccc cggccguacc gcagacauuc caaguggccc 4020
aucuacacgc ucccacuggc aguggcaaga gcacuaaggu gccggcugcg uacgcagccc 4080
aaggguacaa gguacucguc uugaacccau ccguugccgc uaccuuaggg uuuggggcgu 4140
acaugucuaa agcacauggu guugagccua acaucagaac ugggguaagg accaucacca 4200
cgggcgcuuc caucacguau uccaccuacg guaaguuccu ugccgacggu gguugcucug 4260
ggggcgccua ugacaucaua auaugugaug agugccacuc aacugacucg acuuccaucu 4320
ugggcauugg cacaguccug gaccaagcgg agacggcugg agcgcggcuc gucgugcucg 4380
ccaccgcuac gccuccggga ucggucaccg ugccacaucc caauaucgag gagguggccu 4440
ugcccagcac cggagaaauu cccuucuacg gcaaagccau ccccauugag accaucaagg 4500
gggggaggca ccucaucuuc ugccacucca agaagaaaug ugacgagcuc gcugcaaagc 4560
uggugggccu cggaguuaac gcuguugcgu acuaccgggg ucuugaugug uccgucauac 4620
caacaagcgg agaugucguu gucguggcaa cagacgcucu aaugacgggc uucaccggcg 4680
acuuugacuc agugaucgac uguaauacuu gugucaccca gacaguugau uucagcuugg 4740
acccuaccuu caccauugag acgacaaccg ugccccaaga cgcggugucg cguucgcagc 4800
gacgaggcag gacuggcagg ggcaggaugg gcauauacag guuuguggcu ccaggggaac 4860
ggcccucggg cauguucgau ucuucggucc ugugugagug cuaugacgcg ggcugugcuu 4920
gguaugagcu cacgcccgcc gagaccucag ucagguugcg ggcuuaccua aauacaccag 4980
ggcugcccgu cugccaggac caccuggagu uuugggaggg ggucuucaca ggccucaccc 5040
acauagaugc ccauuucuug ucccagacua agcaggcagg agauaacuuc cccuaccugg 5100
uagcauacca ggcuacggug ugcgccaggg cccaggcucc cccuccaucg ugggaucaaa 5160
uguggaagug ucucauacgg cugaagccua cacuacacgg gccaacgccc cuguuguaua 5220
ggcuaggagc cguccagaau gaggucaucc ucacacaucc cauaaccaaa uacaucaugg 5280
caugcauguc ggcugaccua gaggucguca cuagcaccug ggugcugguc ggcggggucc 5340
uugcagcucu ggccgcguac ugccugacga cgggcagcgu ggucauugug ggcaggauca 5400
ucuuguccgg gaagccggcu aucauuccug acagggaagu ccucuaccgg gaguucgaug 5460
aaauggaaga gugugccuca caccuccccu acaucgaaca gggaaugcag cucgccgaac 5520
aauucaagca gaaggcgcuc ggguugcugc agacagccac caagcaagcg gaagccgcug 5580
cuccuguggu ggaguccaag uggcgagccc uugaggccuu cugggcgaag cacaugugga 5640
auuucaucag cgggauacag uacuuagcag gcuuguccac ucugccuggg aaccccgcga 5700
uagcaucacu gauggcauuc acagccucua ucaccagccc gcuuaccacc cuacacaccc 5760
uccuguuuaa caucuuggga ggaugggugg ccgcccaacu ugcccccccc ggugcugccu 5820
cggcuuucgu gggcgccggc auugcuggcg cagcuguugg cagcauaggc cuugggaagg 5880
ugcuugugga cauccuggcg gguuauggag cagggguggc aggcgcgcuc guggccuuca 5940
aggucaugag cggcgagaug cccuccaccg aggaccuggu caacuuacuc ccugccaucc 6000
ucucuccugg ugcccuuguc gucggggucg ugugcgcagc aauacugcgu cggcaugugg 6060
gcccggggga gggggcugug caauggauga accggcugau agcguucgcc ucgcggggua 6120
accacgucuc ccccacgcac uaugugccug agagcgacgc ugcagcgcgu gucacacaga 6180
uccucucuag ccucaccauc acucagcuac ugaagaggcu ccaccagugg auuaauaagg 6240
acugcuccac accaugcucc ggcucguggc uuagggacgu uugggacugg auaugcacgg 6300
uuuugaguga cuucaagacc uggcuccagu ccaagcuccu gccacgguua ccgggaguuc 6360
cauuccuuuc augccaacgu ggguauaagg gggucuggcg gggagauggc aucaugcaga 6420
ccuccugccc auguggagca caaaucgccg gacaugucaa gaacgguucc augaggaucg 6480
uugggccuaa aaccuguagc aacacguggc acggaacauu ccccauuaac gcgcacacca 6540
cgggccccug cacacccucc ccagcgccga acuacucuaa ggcguugugg cggguggcug 6600
cugaggagua cguggaaguc acgcgggugg gggauuucca uuacgugacg ggcaugacca 6660
cugacaacgu aaaaugccca ugccagguuc cggcccccga guucuucaca gagguggaug 6720
ggguacggcu gcacagguac gcuccggcgu gcaaaccucu ccuacgggau gaggucacau 6780
uccaggucgg gcucaaccag uucccgguug ggucacagcu cccaugcgag cccgaaccgg 6840
auguaucagu gcucacuucc augcuuaccg acccuuccca caucacagca gagacggcua 6900
agcguaggcu ggccagaggg ucuucccccu cuuuggccag cucuucagcu agucaguugu 6960
cugcgcccuc auugaaggcg acaugcacca cccaucauga cuccccagac gcugaccuca 7020
uugaggccaa ccuccugugg cggcaggaga ugggagggaa caucacccgu guggagucag 7080
agaacaaggu gguaauccug gacucuuuug acccgcuucg agcggaggag gacgagaggg 7140
aggugucugu ugcggcggag auccugcgga aaaccaggaa guucccccca gcgaugccca 7200
uaugggcacg cccggacuac aacccaccgc ugcuagagac uuggaaggac ccggacuacg 7260
ucccuccagu ggugcacggg ugcccauugc caccuaccaa gaccccucca auaccaccuc 7320
cgcggaggaa aaagacaguu guccugacag aguccaccgu gucuucugcc cuggcggagc 7380
uugccacaaa gaccuuuggc agcuccggau cgucggccgu cgacagcggc acagcgaccg 7440
cccccccuaa ccagcucucc gacgaagugg auacaggauc cgacguugag ucguacuccu 7500
ccaugccccc ccuugaggga gagccggggg accccgaucu cagcgacggg ucuuggucua 7560
cuguaaguga ggaggcuggu gaggacgucg ucugcugcuc gauguccuac acauggacag 7620
gcgccuugau cacgccgugc gccgcggagg agagcaagcu gcccaucaau gcgcugagca 7680
acucuuugcu gcgccaccac aacauggucu augccacaac aucccgcagc gcaagccaac 7740
ggcagaaaaa ggucaccuuu gacagacugc aaguccugga cgaccauuac cgggacgugc 7800
ucaaggagau gaaggcgaag gcguccacag uuaaggcuaa acuucuaucc guagaagagg 7860
ccugcaagcu gacgccccca cacucagcca gguccaaauu uggcuauggg gcgaaggacg 7920
uccggaaccu auccagcaag gccguuaacc acaucaacuc cguguggaag gacuugcugg 7980
aagacacuga gacaccaauu gacaccacca ucauggcaaa aaaugagguc uucuguguuc 8040
aaccagagaa gggaggccgc aagccagcuc gccuuaucgu auacccagac uugggggugc 8100
gugugugcga gaaaauggcc cuuuacgacg uggucuccac ucuuccucag gccgugaugg 8160
gcuccucaua cggauuccag uacucuccug ggcagcgggu cgaguuccug gugaaugccu 8220
ggaaaucaaa gaagaacccu augggcuucg cauaugacac ccgcuguuuu gacucaacgg 8280
ucaccgagaa cgacauccgu guugaggagu caauuuacca auguugugac uuggcccccg 8340
aggccagaca ggugauaagg ucgcucacag agcggcuuua ugucgggggc ccccugacua 8400
auucaaaagg gcagaacugc gguuaucgcc ggugccgcgc cagcggcgug cugacgacua 8460
gcugcgguaa uacccucaca uguuacuuga aggccucugc agccugucga gcugcaaagc 8520
uccaggacug cacgaugcuc gugugcgggg acgaccuugu cguuaucugu gaaagcgcgg 8580
ggacccagga ggacgcggcg agccuacgag ucuucacgga ggcuaugacu agguacuccg 8640
ccccccccgg ggacccgccc cgaccggaau acgacuugga guugauaaca ucaugcuccu 8700
ccaacguguc ggucgcgcac gaugcaucug gcaaacgggu guauuaccuc acccgugacc 8760
ccaccacccc ccuugcgcgg gcugcguggg agacagcuaa acacacucca gucaacuccu 8820
ggcuaggcaa caucaucaug uaugcgccca cccucugggc aaggaugauu cugaugacuc 8880
acuucuucuc cauccuucua gcucaggagc agcuugaaaa agcccuggau ugucagaucu 8940
acggggccac uuacuccauu gaaccacuug accuaccuca gaucauucaa cgacuccaug 9000
gucuuagcgc auucucacuc cauaguuacu cuccagguga aaucaauagg guggcuucau 9060
gccucaggaa acuuggggua ccgcccuugc gagucuggag acaucgggcc agaagugucc 9120
gcgcuaagcu acugucccag ggggggaggg cugccacuug uggcaaguac cucuucaacu 9180
gggcaguaag gaccaagcuc aaacucacuc caaucccggc ugcgucccag uuggacuugu 9240
ccggcugguu cauugcuggu uacagcgggg gagacauaua ucacagccug ucucgugccc 9300
gaccccgcug guuuauguug ugccuacucc uacuuucugu ggggguaggc aucuaccugc 9360
uccccaaucg augaacgggg ggcuaaacac uccaggccaa uaggccauuc uguuuuuuuu 9420
uuuuuuuuuu uuuuuuuuuu uuuuuuuuuu uuuuuuuuuu uuuuuuccuu uuuuuuuuuu 9480
uuuuucccuu ucuuuuggug gcuccaucuu agcccuaguc acggcuagcu gugaaagguc 9540
cgugagccgc augacugcag agagugcuga uacuggccuc ucugcagauc augu 9594
<210>4
<211>3010
<212>PRT
<213>丙型肝炎病毒
<400>4
Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Thr Lys Arg Asn Thr Asn
1 5 10 15
Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gly Gly Gln Ile Val Gly
20 25 30
Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Arg Leu Gly Val Arg Ala
35 40 45
Thr Arg Lys Thr Ser Glu Arg Ser Gln Pro Arg Gly Arg Arg Gln Pro
50 55 60
Ile Pro Lys Ala Arg Gln Pro Glu Gly Arg Ala Trp Ala Gln Pro Gly
65 70 75 80
Tyr Pro Trp Pro Leu Tyr Gly Asn Glu Gly Leu Gly Trp Ala Gly Trp
85 90 95
Leu Leu Ser Pro Arg Gly Ser Arg Pro Ser Trp Gly Pro Thr Asp Pro
100 105 110
Arg Arg Arg Ser Arg Asn Leu Gly Lys Val Ile Asp Thr Leu Thr Cys
115 120 125
Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Leu Val Gly Ala Pro Leu
130 135 140
Gly Gly Ala Ala Arg Ala Leu Ala His Gly Val Arg Val Leu Glu Asp
145 150 155 160
Gly Val Asn Tyr Ala Thr Gly Asn Leu Pro Gly Cys Pro Phe Ser Ile
165 170 175
Phe Leu Leu Ala Leu Leu Ser Cys Leu Thr Ile Pro Ala Ser Ala His
180 185 190
Glu Val Arg Asn Val Ser Gly Leu Tyr His Val Thr Asn Asp Cys Ser
195 200 205
Asn Ser Ser Ile Val Tyr Glu Ala Ala Asp Met Ile Met His Thr Pro
210 215 220
Gly Cys Val Pro Cys Val Arg Glu Gly Asn Ser Ser Arg Cys Trp Val
225 230 235 240
Ala Leu Thr Pro Thr Leu Ala Ala Arg Asn Ser Ser Val Pro Thr Ala
245 250 255
Thr Ile Arg Arg His Val Asp Leu Leu Val Gly Ala Ala Ala Phe Cys
260 265 270
Ser Ala Met Tyr Val Gly Asp Leu Cys Gly Ser Val Phe Leu Val Ser
275 280 285
Gln Leu Phe Thr Phe Ser Pro Arg Arg Tyr Glu Thr Val Gln Asp Cys
290 295 300
Asn Cys Ser Leu Tyr Pro Gly His Val Ser Gly His Arg Met Ala Trp
305 310 315 320
Asp Met Met Met Asn Trp Ser Pro Thr Thr Ala Leu Val Val Ser Gln
325 330 335
Leu Leu Arg Ile Pro Gln Ala Val Val Asp Met Val Val Gly Ala His
340 345 350
Trp Gly Val Leu Ala Gly Leu Ala Tyr Tyr Ser Met Val Gly Asn Trp
355 360 365
Ala Lys Val Leu Ile Val Met Leu Leu Phe Ala Gly Val Asp Gly Lys
370 375 380
Thr Tyr Val Thr Gly Gly Ala Gln Ser Arg Ala Thr Gln Gly Phe Ala
385 390 395 400
Ser Leu Phe Thr Arg Gly Pro Ser Gln Lys Leu Gln Leu Val Asn Ser
405 410 415
Asn Gly Ser Trp His Ile Asn Arg Thr Ala Leu Asn Cys Asn Asp Ser
420 425 430
Phe Gln Thr Gly Phe Leu Ala Ala Leu Phe Tyr Ala His Arg Phe Asn
435 440 445
Ser Ser Gly Cys Pro Glu Arg Met Ala Ser Cys Arg Pro Ile Asp Thr
450 455 460
Phe Asp Gln Gly Trp Gly Pro Ile Thr His Val Ala Arg Arg Thr Ser
465 470 475 480
Asp Gln Arg Pro Tyr Cys Trp His Tyr Ala Pro Gln Pro Cys Gly Ile
485 490 495
Val Pro Ala Leu Gln Val Cys Gly Pro Val Tyr Cys Phe Thr Pro Ser
500 505 510
Pro Val Val Val Gly Thr Thr Asp Arg Phe Gly Ala Pro Thr Tyr Asn
515 520 525
Trp Gly Glu Asn Glu Thr Asp Val Leu Leu Leu Asn Asn Thr Arg Pro
530 535 540
Pro His Gly Asn Trp Phe Gly Cys Thr Trp Met Asn Ser Thr Gly Phe
545 550 555 560
Thr Lys Thr Cys Gly Gly Pro Pro Cys Asn Ile Gly Gly Phe Gly Asn
565 570 575
Asn Thr Leu Thr Cys Pro Thr Asp Cys Phe Arg Lys His Pro Glu Ala
580 585 590
Thr Tyr Thr Lys Cys Gly Ser Gly Pro Trp Leu Thr Pro Arg Cys Met
595 600 605
Val Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe
610 615 620
Ser Ile Phe Lys Val Arg Met Tyr Val Gly Gly Val Glu His Arg Leu
625 630 635 640
Thr Ala Ala Cys Asn Trp Thr Arg Gly Glu Arg Cys Asn Leu Glu Asp
645 650 655
Arg Asp Arg Ser Glu Leu Ser Pro Leu Leu Leu Ser Thr Thr Glu Trp
660 665 670
Gln Val Leu Pro Cys Ser Phe Thr Thr Leu Pro Ala Leu Ser Thr Gly
675 680 685
Leu Ile His Leu His Gln Asn Ile Val Asp Val Gln Tyr Leu Tyr Gly
690 695 700
Val Gly Ser Ser Val Val Ser Ile Ala Ile Arg Trp Glu Tyr Val Val
705 710 715 720
Leu Leu Phe Leu Leu Leu Ala Asp Ala Arg Val Cys Ala Cys Leu Trp
725 730 735
Met Met Leu Leu Ile Ala Gln Ala Glu Ala Ala Leu Glu Asn Leu Val
740 745 750
Ile Leu Asn Ala Ala Ser Val Ala Gly Ala His Gly Val Leu Ser Phe
755 760 765
Leu Val Phe Phe Cys Ala Ala Trp Tyr Ile Lys Gly Lys Leu Val Pro
770 775 780
Gly Ala Ala Tyr Ala Phe Tyr Gly Val Trp Pro Leu Leu Leu Leu Leu
785 790 795 800
Leu Ser Leu Pro Pro Arg Ala Tyr Ala Leu Asp Arg Glu Met Ala Ala
805 810 815
Ser Cys Gly Gly Ala Val Phe Val Gly Leu Met Leu Leu Thr Leu Ser
820 825 830
Pro His Tyr Lys Val Phe Leu Ala Arg Leu Ile Trp Trp Leu Gln Tyr
835 840 845
Phe Ile Thr Arg Ala Glu Ala His Leu Gln Val Trp Val Pro Pro Leu
850 855 860
Asn Val Arg Gly Gly Arg Asp Ala Ile Ile Leu Leu Thr Cys Val Val
865 870 875 880
His Pro Glu Leu Ile Phe Asp Ile Thr Lys Ile Leu Leu Ala Met Leu
885 890 895
Gly Pro Leu Met Val Leu Gln Ala Gly Leu Thr Arg Val Pro Tyr Phe
900 905 910
Val Arg Ala Gln Gly Leu Ile Arg Ala Cys Met Leu Val Arg Lys Val
915 920 925
Ala Gly Gly His Tyr Val Gln Met Ala Leu Met Lys Leu Ala Ala Leu
930 935 940
Thr Gly Thr Tyr Val Tyr Asp His Leu Thr Pro Leu Gln Asp Trp Ala
945 950 955 960
His Ala Gly Leu Arg Asp Leu Ala Val Ala Val Glu Pro Val Val Phe
965 970 975
Ser Asp Met Glu Thr Lys Val Ile Thr Trp Gly Ala Asp Thr Ala Ala
980 985 990
Cys Gly Asp Ile Ile Ser Gly Leu Pro Val Ser Ala Arg Arg Gly Arg
995 1000 1005
Glu Ile Leu Leu Gly Pro Ala Asp Arg Phe Gly Glu Gln Gly Trp
1010 1015 1020
Arg Leu Leu Ala Pro Ile Thr Ala Tyr Ala Gln Gln Thr Arg Gly
1025 1030 1035
Leu Leu Gly Cys Ile Ile Thr Ser Leu Thr Gly Arg Asp Lys Asn
1040 1045 1050
Gln Val Glu Gly Glu Val Gln Val Val Ser Thr Ala Thr Gln Ser
1055 1060 1065
Phe Leu Ala Thr Cys Val Asn Gly Val Cys Trp Thr Val Tyr His
1070 1075 1080
Gly Ala Gly Ser Lys Thr Leu Ala Gly Pro Lys Gly Pro Ile Thr
1085 1090 1095
Gln Met Tyr Thr Asn Val Asp Gln Asp Leu Val Gly Trp Pro Ala
1100 1105 1110
Pro Pro Gly Ala Arg Ser Leu Thr Pro Cys Thr Cys Gly Ser Ser
1115 1120 1125
Asp Leu Tyr Leu Val Thr Arg His Ala Asp Val Ile Pro Val Arg
1130 1135 1140
Arg Arg Gly Asp Ser Arg Gly Ser Leu Leu Ser Pro Arg Pro Ile
1145 1150 1155
Ser Tyr Leu Lys Gly Ser Ser Gly Gly Pro Leu Leu Cys Pro Leu
1160 1165 1170
Gly His Ala Val Gly Ile Phe Arg Ala Ala Val Cys Thr Arg Gly
1175 1180 1185
Val Ala Lys Ala Val Asp Phe Val Pro Val Glu Ser Met Glu Thr
1190 1195 1200
Thr Met Arg Ser Pro Val Phe Thr Asp Asn Ser Ser Pro Pro Ala
1205 1210 1215
Val Pro Gln Thr Phe Gln Val Ala His Leu His Ala Pro Thr Gly
1220 1225 1230
Ser Gly Lys Ser Thr Lys Val Pro Ala Ala Tyr Ala Ala Gln Gly
1235 1240 1245
Tyr Lys Val Leu Val Leu Asn Pro Ser Val Ala Ala Thr Leu Gly
1250 1255 1260
Phe Gly Ala Tyr Met Ser Lys Ala His Gly Val Glu Pro Asn Ile
1265 1270 1275
Arg Thr Gly Val Arg Thr Ile Thr Thr Gly Ala Ser Ile Thr Tyr
1280 1285 1290
Ser Thr Tyr Gly Lys Phe Leu Ala Asp Gly Gly Cys Ser Gly Gly
1295 1300 1305
Ala Tyr Asp Ile Ile Ile Cys Asp Glu Cys His Ser Thr Asp Ser
1310 1315 1320
Thr Ser Ile Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr
1325 1330 1335
Ala Gly Ala Arg Leu Val Val Leu Ala Thr Ala Thr Pro Pro Gly
1340 1345 1350
Ser Val Thr Val Pro His Pro Asn Ile Glu Glu Val Ala Leu Pro
1355 1360 1365
Ser Thr Gly Glu Ile Pro Phe Tyr Gly Lys Ala Ile Pro Ile Glu
1370 1375 1380
Thr Ile Lys Gly Gly Arg His Leu Ile Phe Cys His Ser Lys Lys
1385 1390 1395
Lys Cys Asp Glu Leu Ala Ala Lys Leu Val Gly Leu Gly Val Asn
1400 1405 1410
Ala Val Ala Tyr Tyr Arg Gly Leu Asp Val Ser Val Ile Pro Thr
1415 1420 1425
Ser Gly Asp Val Val Val Val Ala Thr Asp Ala Leu Met Thr Gly
1430 1435 1440
Phe Thr Gly Asp Phe Asp Ser Val Ile Asp Cys Asn Thr Cys Val
1445 1450 1455
Thr Gln Thr Val Asp Phe Ser Leu Asp Pro Thr Phe Thr Ile Glu
1460 1465 1470
Thr Thr Thr Val Pro Gln Asp Ala Val Ser Arg Ser Gln Arg Arg
1475 1480 1485
Gly Arg Thr Gly Arg Gly Arg Met Gly Ile Tyr Arg Phe Val Ala
1490 1495 1500
Pro Gly Glu Arg Pro Ser Gly Met Phe Asp Ser Ser Val Leu Cys
1505 1510 1515
Glu Cys Tyr Asp Ala Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala
1520 1525 1530
Glu Thr Ser Val Arg Leu Arg Ala Tyr Leu Asn Thr Pro Gly Leu
1535 1540 1545
Pro Val Cys Gln Asp His Leu Glu Phe Trp Glu Gly Val Phe Thr
1550 1555 1560
Gly Leu Thr His Ile Asp Ala His Phe Leu Ser Gln Thr Lys Gln
1565 1570 1575
Ala Gly Asp Asn Phe Pro Tyr Leu Val Ala Tyr Gln Ala Thr Val
1580 1585 1590
Cys Ala Arg Ala Gln Ala Pro Pro Pro Ser Trp Asp Gln Met Trp
1595 1600 1605
Lys Cys Leu Ile Arg Leu Lys Pro Thr Leu His Gly Pro Thr Pro
1610 1615 1620
Leu Leu Tyr Arg Leu Gly Ala Val Gln Asn Glu Val Ile Leu Thr
1625 1630 1635
His Pro Ile Thr Lys Tyr Ile Met Ala Cys Met Ser Ala Asp Leu
1640 1645 1650
Glu Val Val Thr Ser Thr Trp Val Leu Val Gly Gly Val Leu Ala
1655 1660 1665
Ala Leu Ala Ala Tyr Cys Leu Thr Thr Gly Ser Val Val Ile Val
1670 1675 1680
Gly Arg Ile Ile Leu Ser Gly Lys Pro Ala Ile Ile Pro Asp Arg
1685 1690 1695
Glu Val Leu Tyr Arg Glu Phe Asp Glu Met Glu Glu Cys Ala Ser
1700 1705 1710
His Leu Pro Tyr Ile Glu Gln Gly Met Gln Leu Ala Glu Gln Phe
1715 1720 1725
Lys Gln Lys Ala Leu Gly Leu Leu Gln Thr Ala Thr Lys Gln Ala
1730 1735 1740
Glu Ala Ala Ala Pro Val Val Glu Ser Lys Trp Arg Ala Leu Glu
1745 1750 1755
Ala Phe Trp Ala Lys His Met Trp Asn Phe Ile Ser Gly Ile Gln
1760 1765 1770
Tyr Leu Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Ile Ala
1775 1780 1785
Ser Leu Met Ala Phe Thr Ala Ser Ile Thr Ser Pro Leu Thr Thr
1790 1795 1800
Leu His Thr Leu Leu Phe Asn Ile Leu Gly Gly Trp Val Ala Ala
1805 1810 1815
Gln Leu Ala Pro Pro Gly Ala Ala Ser Ala Phe Val Gly Ala Gly
1820 1825 1830
Ile Ala Gly Ala Ala Val Gly Ser Ile Gly Leu Gly Lys Val Leu
1835 1840 1845
Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu
1850 1855 1860
Val Ala Phe Lys Val Met Ser Gly Glu Met Pro Ser Thr Glu Asp
1865 1870 1875
Leu Val Asn Leu Leu Pro Ala Ile Leu Ser Pro Gly Ala Leu Val
1880 1885 1890
Val Gly Val Val Cys Ala Ala Ile Leu Arg Arg His Val Gly Pro
1895 1900 1905
Gly Glu Gly Ala Val Gln Trp Met Asn Arg Leu Ile Ala Phe Ala
1910 1915 1920
Ser Arg Gly Asn His Val Ser Pro Thr His Tyr Val Pro Glu Ser
1925 1930 1935
Asp Ala Ala Ala Arg Val Thr Gln Ile Leu Ser Ser Leu Thr Ile
1940 1945 1950
Thr Gln Leu Leu Lys Arg Leu His Gln Trp Ile Asn Lys Asp Cys
1955 1960 1965
Ser Thr Pro Cys Ser Gly Ser Trp Leu Arg Asp Val Trp Asp Trp
1970 1975 1980
Ile Cys Thr Val Leu Ser Asp Phe Lys Thr Trp Leu Gln Ser Lys
1985 1990 1995
Leu Leu Pro Arg Leu Pro Gly Val Pro Phe Leu Ser Cys Gln Arg
2000 2005 2010
Gly Tyr Lys Gly Val Trp Arg Gly Asp Gly Ile Met Gln Thr Ser
2015 2020 2025
Cys Pro Cys Gly Ala Gln Ile Ala Gly His Val Lys Asn Gly Ser
2030 2035 2040
Met Arg Ile Val Gly Pro Lys Thr Cys Ser Asn Thr Trp His Gly
2045 2050 2055
Thr Phe Pro Ile Asn Ala His Thr Thr Gly Pro Cys Thr Pro Ser
2060 2065 2070
Pro Ala Pro Asn Tyr Ser Lys Ala Leu Trp Arg Val Ala Ala Glu
2075 2080 2085
Glu Tyr Val Glu Val Thr Arg Val Gly Asp Phe His Tyr Val Thr
2090 2095 2100
Gly Met Thr Thr Asp Asn Val Lys Cys Pro Cys Gln Val Pro Ala
2105 2110 2115
Pro Glu Phe Phe Thr Glu Val Asp Gly Val Arg Leu His Arg Tyr
2120 2125 2130
Ala Pro Ala Cys Lys Pro Leu Leu Arg Asp Glu Val Thr Phe Gln
2135 2140 2145
Val Gly Leu Asn Gln Phe Pro Val Gly Ser Gln Leu Pro Cys Glu
2150 2155 2160
Pro Glu Pro Asp Val Ser Val Leu Thr Ser Met Leu Thr Asp Pro
2165 2170 2175
Ser His Ile Thr Ala Glu Thr Ala Lys Arg Arg Leu Ala Arg Gly
2180 2185 2190
Ser Ser Pro Ser Leu Ala Ser Ser Ser Ala Ser Gln Leu Ser Ala
2195 2200 2205
Pro Ser Leu Lys Ala Thr Cys Thr Thr His His Asp Ser Pro Asp
2210 2215 2220
Ala Asp Leu Ile Glu Ala Asn Leu Leu Trp Arg Gln Glu Met Gly
2225 2230 2235
Gly Asn Ile Thr Arg Val Glu Ser Glu Asn Lys Val Val Ile Leu
2240 2245 2250
Asp Ser Phe Asp Pro Leu Arg Ala Glu Glu Asp Glu Arg Glu Val
2255 2260 2265
Ser Val Ala Ala Glu Ile Leu Arg Lys Thr Arg Lys Phe Pro Pro
2270 2275 2280
Ala Met Pro Ile Trp Ala Arg Pro Asp Tyr Asn Pro Pro Leu Leu
2285 2290 2295
Glu Thr Trp Lys Asp Pro Asp Tyr Val Pro Pro Val Val His Gly
2300 2305 2310
Cys Pro Leu Pro Pro Thr Lys Thr Pro Pro Ile Pro Pro Pro Arg
2315 2320 2325
Arg Lys Lys Thr Val Val Leu Thr Glu Ser Thr Val Ser Ser Ala
2330 2335 2340
Leu Ala Glu Leu Ala Thr Lys Thr Phe Gly Ser Ser Gly Ser Ser
2345 2350 2355
Ala Val Asp Ser Gly Thr Ala Thr Ala Pro Pro Asn Gln Leu Ser
2360 2365 2370
Asp Glu Val Asp Thr Gly Ser Asp Val Glu Ser Tyr Ser Ser Met
2375 2380 2385
Pro Pro Leu Glu Gly Glu Pro Gly Asp Pro Asp Leu Ser Asp Gly
2390 2395 2400
Ser Trp Ser Thr Val Ser Glu Glu Ala Gly Glu Asp Val Val Cys
2405 2410 2415
Cys Ser Met Ser Tyr Thr Trp Thr Gly Ala Leu Ile Thr Pro Cys
2420 2425 2430
Ala Ala Glu Glu Ser Lys Leu Pro Ile Asn Ala Leu Ser Asn Ser
2435 2440 2445
Leu Leu Arg His His Asn Met Val Tyr Ala Thr Thr Ser Arg Ser
2450 2455 2460
Ala Ser Gln Arg Gln Lys Lys Val Thr Phe Asp Arg Leu Gln Val
2465 2470 2475
Leu Asp Asp His Tyr Arg Asp Val Leu Lys Glu Met Lys Ala Lys
2480 2485 2490
Ala Ser Thr Val Lys Ala Lys Leu Leu Ser Val Glu Glu Ala Cys
2495 2500 2505
Lys Leu Thr Pro Pro His Ser Ala Arg Ser Lys Phe Gly Tyr Gly
2510 2515 2520
Ala Lys Asp Val Arg Asn Leu Ser Ser Lys Ala Val Asn His Ile
2525 2530 2535
Asn Ser Val Trp Lys Asp Leu Leu Glu Asp Thr Glu Thr Pro Ile
2540 2545 2550
Asp Thr Thr Ile Met Ala Lys Asn Glu Val Phe Cys Val Gln Pro
2555 2560 2565
Glu Lys Gly Gly Arg Lys Pro Ala Arg Leu Ile Val Tyr Pro Asp
2570 2575 2580
Leu Gly Val Arg Val Cys Glu Lys Met Ala Leu Tyr Asp Val Val
2585 2590 2595
Ser Thr Leu Pro Gln Ala Val Met Gly Ser Ser Tyr Gly Phe Gln
2600 2605 2610
Tyr Ser Pro Gly Gln Arg Val Glu Phe Leu Val Asn Ala Trp Lys
2615 2620 2625
Ser Lys Lys Asn Pro Met Gly Phe Ala Tyr Asp Thr Arg Cys Phe
2630 2635 2640
Asp Ser Thr Val Thr Glu Asn Asp Ile Arg Val Glu Glu Ser Ile
2645 2650 2655
Tyr Gln Cys Cys Asp Leu Ala Pro Glu Ala Arg Gln Val Ile Arg
2660 2665 2670
Ser Leu Thr Glu Arg Leu Tyr Val Gly Gly Pro Leu Thr Asn Ser
2675 2680 2685
Lys Gly Gln Asn Cys Gly Tyr Arg Arg Cys Arg Ala Ser Gly Val
2690 2695 2700
Leu Thr Thr Ser Cys Gly Asn Thr Leu Thr Cys Tyr Leu Lys Ala
2705 2710 2715
Ser Ala Ala Cys Arg Ala Ala Lys Leu Gln Asp Cys Thr Met Leu
2720 2725 2730
Val Cys Gly Asp Asp Leu Val Val Ile Cys Glu Ser Ala Gly Thr
2735 2740 2745
Gln Glu Asp Ala Ala Ser Leu Arg Val Phe Thr Glu Ala Met Thr
2750 2755 2760
Arg Tyr Ser Ala Pro Pro Gly Asp Pro Pro Arg Pro Glu Tyr Asp
2765 2770 2775
Leu Glu Leu Ile Thr Ser Cys Ser Ser Asn Val Ser Val Ala His
2780 2785 2790
Asp Ala Ser Gly Lys Arg Val Tyr Tyr Leu Thr Arg Asp Pro Thr
2795 2800 2805
Thr Pro Leu Ala Arg Ala Ala Trp Glu Thr Ala Lys His Thr Pro
2810 2815 2820
Val Asn Ser Trp Leu Gly Asn Ile Ile Met Tyr Ala Pro Thr Leu
2825 2830 2835
Trp Ala Arg Met Ile Leu Met Thr His Phe Phe Ser Ile Leu Leu
2840 2845 2850
Ala Gln Glu Gln Leu Glu Lys Ala Leu Asp Cys Gln Ile Tyr Gly
2855 2860 2865
Ala Thr Tyr Ser Ile Glu Pro Leu Asp Leu Pro Gln Ile Ile Gln
2870 2875 2880
Arg Leu His Gly Leu Ser Ala Phe Ser Leu His Ser Tyr Ser Pro
2885 2890 2895
Gly Glu Ile Asn Arg Val Ala Ser Cys Leu Arg Lys Leu Gly Val
2900 2905 2910
Pro Pro Leu Arg Val Trp Arg His Arg Ala Arg Ser Val Arg Ala
2915 2920 2925
Lys Leu Leu Ser Gln Gly Gly Arg Ala Ala Thr Cys Gly Lys Tyr
2930 2935 2940
Leu Phe Asn Trp Ala Val Arg Thr Lys Leu Lys Leu Thr Pro Ile
2945 2950 2955
Pro Ala Ala Ser Gln Leu Asp Leu Ser Gly Trp Phe Ile Ala Gly
2960 2965 2970
Tyr Ser Gly Gly Asp Ile Tyr His Ser Leu Ser Arg Ala Arg Pro
2975 2980 2985
Arg Trp Phe Met Leu Cys Leu Leu Leu Leu Ser Val Gly Val Gly
2990 2995 3000
Ile Tyr Leu Leu Pro Asn Arg
3005 3010
<210>5
<211>783
<212>RNA
<213>丙型肝炎病毒
<400>5
gccucacacc uccccuacau cgaacaggga augcagcucg ccgaacaauu caagcagaag 60
gcgcucgggu ugcugcagac agccaccaag caagcggaag ccgcugcucc ugugguggag 120
uccaaguggc gagcccuuga ggccuucugg gcgaagcaca uguggaauuu caucagcggg 180
auacaguacu uagcaggcuu guccacucug ccugggaacc ccgcgauagc aucacugaug 240
gcauucacag ccucuaucac cagcccgcuu accacccaac acacccuccu guuuaacauc 300
uugggaggau ggguggccgc ccaacuugcc ccccccggug cugccucggc uuucgugggc 360
gccggcauug cuggcgcagc uguuggcagc auaggccuug ggaaggugcu uguggacauc 420
cuggcggguu auggagcagg gguggcaggc gcgcucgugg ccuucaaggu caugagcggc 480
gagaugcccu ccaccgagga ccuggucaac uuacucccug ccauccucuc uccuggugcc 540
cuugucgucg gggucgugug cgcagcaaua cugcgucggc augugggccc gggggagggg 600
gcugugcaau ggaugaaccg gcugauagcg uucgccucgc gggguaacca cgucuccccc 660
acgcacuaug ugccugagag cgacgcugca gcgcguguca cacagauccu cucuagccuc 720
accaucacuc agcuacugaa gaggcuccac caguggauua augaggacug cuccacacca 780
ugc 783
<210>6
<211>261
<212>PRT
<213>丙型肝炎病毒
<400>6
Ala Ser His Leu Pro Tyr Ile Glu Gln Gly Met Gln Leu Ala Glu Gln
1 5 10 15
Phe Lys Gln Lys Ala Leu Gly Leu Leu Gln Thr Ala Thr Lys Gln Ala
20 25 30
Glu Ala Ala Ala Pro Val Val Glu Ser Lys Trp Arg Ala Leu Glu Ala
35 40 45
Phe Trp Ala Lys His Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu
50 55 60
Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Ile Ala Ser Leu Met
65 70 75 80
Ala Phe Thr Ala Ser Ile Thr Ser Pro Leu Thr Thr Gln His Thr Leu
85 90 95
Leu Phe Asn Ile Leu Gly Gly Trp Val Ala Ala Gln Leu Ala Pro Pro
100 105 110
Gly Ala Ala Ser Ala Phe Val Gly Ala Gly Ile Ala Gly Ala Ala Val
115 120 125
Gly Ser Ile Gly Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr
130 135 140
Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys Val Met Ser Gly
145 150 155 160
Glu Met Pro Ser Thr Glu Asp Leu Val Asn Leu Leu Pro Ala Ile Leu
165 170 175
Ser Pro Gly Ala Leu Val Val Gly Val Val Cys Ala Ala Ile Leu Arg
180 185 190
Arg His Val Gly Pro Gly Glu Gly Ala Val Gln Trp Met Asn Arg Leu
195 200 205
Ile Ala Phe Ala Ser Arg Gly Asn His Val Ser Pro Thr His Tyr Val
210 215 220
Pro Glu Ser Asp Ala Ala Ala Arg Val Thr Gln Ile Leu Ser Ser Leu
225 230 235 240
Thr Ile Thr Gln Leu Leu Lys Arg Leu His Gln Trp Ile Asn Glu Asp
245 250 255
Cys Ser Thr Pro Cys
260
<210>7
<211>783
<212>RNA
<213>丙型肝炎病毒
<400>7
gccucacacc uccccuacau cgaacaggga augcagcucg ccgaacaauu caagcagaag 60
gcgcucgggu ugcugcagac agccaccaag caagcggaag ccgcugcucc ugugguggag 120
uccaaguggc gagcccuuga ggccuucugg gcgaagcaca uguggaauuu caucagcggg 180
auacaguacu uagcaggcuu guccacucug ccugggaacc ccgcgauagc aucacugaug 240
gcauucacag ccucuaucac cagcccgcuu accacccuac acacccuccu guuuaacauc 300
uugggaggau ggguggccgc ccaacuugcc ccccccggug cugccucggc uuucgugggc 360
gccggcauug cuggcgcagc uguuggcagc auaggccuug ggaaggugcu uguggacauc 420
cuggcggguu auggagcagg gguggcaggc gcgcucgugg ccuucaaggu caugagcggc 480
gagaugcccu ccaccgagga ccuggucaac uuacucccug ccauccucuc uccuggugcc 540
cuugucgucg gggucgugug cgcagcaaua cugcgucggc augugggccc gggggagggg 600
gcugugcaau ggaugaaccg gcugauagcg uucgccucgc gggguaacca cgucuccccc 660
acgcacuaug ugccugagag cgacgcugca gcgcguguca cacagauccu cucuagccuc 720
accaucacuc agcuacugaa gaggcuccac caguggauua auaaggacug cuccacacca 780
ugc 783
<210>8
<211>261
<212>PRT
<213>丙型肝炎病毒
<400>8
Ala Ser His Leu Pro Tyr Ile Glu Gln Gly Met Gln Leu Ala Glu Gln
1 5 10 15
Phe Lys Gln Lys Ala Leu Gly Leu Leu Gln Thr Ala Thr Lys Gln Ala
20 25 30
Glu Ala Ala Ala Pro Val Val Glu Ser Lys Trp Arg Ala Leu Glu Ala
35 40 45
Phe Trp Ala Lys His Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu
50 55 60
Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Ile Ala Ser Leu Met
65 70 75 80
Ala Phe Thr Ala Ser Ile Thr Ser Pro Leu Thr Thr Leu His Thr Leu
85 90 95
Leu Phe Asn Ile Leu Gly Gly Trp Val Ala Ala Gln Leu Ala Pro Pro
100 105 110
Gly Ala Ala Ser Ala Phe Val Gly Ala Gly Ile Ala Gly Ala Ala Val
115 120 125
Gly Ser Ile Gly Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr
130 135 140
Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys Val Met Ser Gly
145 150 155 160
Glu Met Pro Ser Thr Glu Asp Leu Val Asn Leu Leu Pro Ala Ile Leu
165 170 175
Ser Pro Gly Ala Leu Val Val Gly Val Val Cys Ala Ala Ile Leu Arg
180 185 190
Arg His Val Gly Pro Gly Glu Gly Ala Val Gln Trp Met Asn Arg Leu
195 200 205
Ile Ala Phe Ala Ser Arg Gly Asn His Val Ser Pro Thr His Tyr Val
210 215 220
Pro Glu Ser Asp Ala Ala Ala Arg Val Thr Gln Ile Leu Ser Ser Leu
225 230 235 240
Thr Ile Thr Gln Leu Leu Lys Arg Leu His Gln Trp Ile Asn Lys Asp
245 250 255
Cys Ser Thr Pro Cys
260
<210>9
<211>8010
<212>RNA
<213>人工序列
<220>
<223>亚基因组HCV RNA复制子
<400>9
uaauacgacu cacuauagcc agcccccgau ugggggcgac acuccaccau agaucacucc 60
ccugugagga acuacugucu ucacgcagaa agcgucuagc cauggcguua guaugagugu 120
cgugcagccu ccaggacccc cccucccggg agagccauag uggucugcgg aaccggugag 180
uacaccggaa uugccaggac gaccgggucc uuucuuggau caacccgcuc aaugccugga 240
gauuugggcg ugcccccgcg agacugcuag ccgaguagug uugggucgcg aaaggccuug 300
ugguacugcc ugauagggug cuugcgagug ccccgggagg ucucguagac cgugcaccau 360
gagcacgaau ccuaaaccuc aaagaaaaac caaacguaac accaacgggc gcgccaugau 420
ugaacaagau ggauugcacg cagguucucc ggccgcuugg guggagaggc uauucggcua 480
ugacugggca caacagacaa ucggcugcuc ugaugccgcc guguuccggc ugucagcgca 540
ggggcgcccg guucuuuuug ucaagaccga ccuguccggu gcccugaaug aacugcagga 600
cgaggcagcg cggcuaucgu ggcuggccac gacgggcguu ccuugcgcag cugugcucga 660
cguugucacu gaagcgggaa gggacuggcu gcuauugggc gaagugccgg ggcaggaucu 720
ccugucaucu caccuugcuc cugccgagaa aguauccauc auggcugaug caaugcggcg 780
gcugcauacg cuugauccgg cuaccugccc auucgaccac caagcgaaac aucgcaucga 840
gcgagcacgu acucggaugg aagccggucu ugucgaucag gaugaucugg acgaagagca 900
ucaggggcuc gcgccagccg aacuguucgc caggcucaag gcgcgcaugc ccgacggcga 960
ggaucucguc gugacccaug gcgaugccug cuugccgaau aucauggugg aaaauggccg 1020
cuuuucugga uucaucgacu guggccggcu ggguguggcg gaccgcuauc aggacauagc 1080
guuggcuacc cgugauauug cugaagagcu uggcggcgaa ugggcugacc gcuuccucgu 1140
gcuuuacggu aucgccgcuc ccgauucgca gcgcaucgcc uucuaucgcc uucuugacga 1200
guucuucuga guuuaaacag accacaacgg uuucccucua gcgggaucaa uuccgccccu 1260
cucccucccc ccccccuaac guuacuggcc gaagccgcuu ggaauaaggc cggugugcgu 1320
uugucuauau guuauuuucc accauauugc cgucuuuugg caaugugagg gcccggaaac 1380
cuuggcccug ucuucuugac gagcauuccu aggggucuuu ccccucucgc caaaggaaug 1440
caaggucugu uggaugucgu gaaggaagca guuccucugg gaagcuucuu gaagacaaac 1500
aacgucugua gcgacccuuu gcaggcagcg gaacccccca ccuggcgaca ggugccucug 1560
cggccaaaag ccacguguau aagauacacc ugcaaaggcg guacaacccc agugccacgu 1620
ugugaguugg auaguugugg aaagagucaa auggcucucc ucaagcguau ucaacaaggg 1680
gcugaaggau gcccagaagg uaccccauug uaugggaucu gaucuggggc cucggugcac 1740
augcucuaca uguguuuagu cgagguuaaa aaaacgucua ggccccccga accacgggga 1800
cgugguuuuc cuuugaaaaa cacgauaaua ccauggcgcc uaucacggcu uacgcucaac 1860
agacgcgggg ccuacuuggc uguaucauca ccagccucac aggccgggac aagaaccagg 1920
ucgaggggga gguucaggug guuuccaccg caacgcaauc uuuccuggcg accugcguca 1980
acggcgugug uuggacuguc uaccauggug ccggcucgaa gacccuggcc ggcccgaagg 2040
gcccaaucac ccaaauguac accaaugugg accaagaccu cgucggcugg ccggcgcccc 2100
ccggggcgcg cucccugaca ccgugcaccu gcggcagcuc ggaccucuac cuggucacga 2160
ggcaugcuga ugucauuccg gugcgccggc ggggcgacag cagggggagu cuacucucuc 2220
ccaggcccau cuccuacuua aagggcuccu cagguggucc acugcuuugc ccccuggggc 2280
acgcuguggg caucuuccgg gccgcugugu gcacccgggg gguugcaaag gcgguggauu 2340
uuguaccugu ugagucuaug gaaaccacca ugcggucucc ggucuuuacg gauaauucau 2400
cucccccggc cguaccgcag acauuccaag uggcccaucu acacgcuccc acuggcagug 2460
gcaagagcac uaaggugccg gcugcguacg cagcccaagg guacaaggua cucgucuuga 2520
acccauccgu ugccgcuacc uuaggguuug gggcguacau gucuaaagca caugguguug 2580
agccuaacau cagaacuggg guaaggacca ucaccacggg cgcuuccauc acguauucca 2640
ccuacgguaa guuccuugcc gacggugguu gcucuggggg cgccuaugac aucauaauau 2700
gugaugagug ccacucaacu gacucgacuu ccaucuuggg cauuggcaca guccuggacc 2760
aagcggagac ggcuggagcg cggcucgucg ugcucgccac cgcuacgccu ccgggaucgg 2820
ucaccgugcc acaucccaau aucgaggagg uggccuugcc cagcaccgga gaaauucccu 2880
ucuacggcaa agccaucccc auugagacca ucaagggggg gaggcaccuc aucuucugcc 2940
acuccaagaa gaaaugugac gagcucgcug caaagcuggu gggccucgga guuaacgcug 3000
uugcguacua ccggggucuu gauguguccg ucauaccaac aagcggagau gucguugucg 3060
uggcaacaga cgcucuaaug acgggcuuca ccggcgacuu ugacucagug aucgacugua 3120
auacuugugu cacccagaca guugauuuca gcuuggaccc uaccuucacc auugagacga 3180
caaccgugcc ccaagacgcg gugucgcguu cgcagcgacg aggcaggacu ggcaggggca 3240
ggaugggcau auacagguuu guggcuccag gggaacggcc cucgggcaug uucgauucuu 3300
cgguccugug ugagugcuau gacgcgggcu gugcuuggua ugagcucacg cccgccgaga 3360
ccucagucag guugcgggcu uaccuaaaua caccagggcu gcccgucugc caggaccacc 3420
uggaguuuug ggaggggguc uucacaggcc ucacccacau agaugcccau uucuuguccc 3480
agacuaagca ggcaggagau aacuuccccu accugguagc auaccaggcu acggugugcg 3540
ccagggccca ggcucccccu ccaucguggg aucaaaugug gaagugucuc auacggcuga 3600
agccuacacu acacgggcca acgccccugu uguauaggcu aggagccguc cagaaugagg 3660
ucauccucac acaucccaua accaaauaca ucauggcaug caugucggcu gaccuagagg 3720
ucgucacuag caccugggug cuggucggcg ggguccuugc agcucuggcc gcguacugcc 3780
ugacgacggg cagcgugguc auugugggca ggaucaucuu guccgggaag ccggcuauca 3840
uuccugacag ggaaguccuc uaccgggagu ucgaugaaau ggaagagugu gccucacacc 3900
uccccuacau cgaacaggga augcagcucg ccgaacaauu caagcagaag gcgcucgggu 3960
ugcugcagac agccaccaag caagcggaag ccgcugcucc ugugguggag uccaaguggc 4020
gagcccuuga ggccuucugg gcgaagcaca uguggaauuu caucagcggg auacaguacu 4080
uagcaggcuu guccacucug ccugggaacc ccgcgauagc aucacugaug gcauucacag 4140
ccucuaucac cagcccgcuu accacccaac acacccuccu guuuaacauc uugggaggau 4200
ggguggccgc ccaacuugcc ccccccggug cugccucggc uuucgugggc gccggcauug 4260
cuggcgcagc uguuggcagc auaggccuug ggaaggugcu uguggacauc cuggcggguu 4320
auggagcagg gguggcaggc gcgcucgugg ccuucaaggu caugagcggc gagaugcccu 4380
ccaccgagga ccuggucaac uuacucccug ccauccucuc uccuggugcc cuugucgucg 4440
gggucgugug cgcagcaaua cugcgucggc augugggccc gggggagggg gcugugcaau 4500
ggaugaaccg gcugauagcg uucgccucgc gggguaacca cgucuccccc acgcacuaug 4560
ugccugagag cgacgcugca gcgcguguca cacagauccu cucuagccuc accaucacuc 4620
agcuacugaa gaggcuccac caguggauua augaggacug cuccacacca ugcuccggcu 4680
cguggcuuag ggacguuugg gacuggauau gcacgguuuu gagugacuuc aagaccuggc 4740
uccaguccaa gcuccugcca cgguuaccgg gaguuccauu ccuuucaugc caacgugggu 4800
auaagggggu cuggcgggga gauggcauca ugcagaccuc cugcccaugu ggagcacaaa 4860
ucgccggaca ugucaagaac gguuccauga ggaucguugg gccuaaaacc uguagcaaca 4920
cguggcacgg aacauucccc auuaacgcgc acaccacggg ccccugcaca cccuccccag 4980
cgccgaacua cucuaaggcg uuguggcggg uggcugcuga ggaguacgug gaagucacgc 5040
ggguggggga uuuccauuac gugacgggca ugaccacuga caacguaaaa ugcccaugcc 5100
agguuccggc ccccgaguuc uucacagagg uggauggggu acggcugcac agguacgcuc 5160
cggcgugcaa accucuccua cgggaugagg ucacauucca ggucgggcuc aaccaguucc 5220
cgguuggguc acagcuccca ugcgagcccg aaccggaugu aucagugcuc acuuccaugc 5280
uuaccgaccc uucccacauc acagcagaga cggcuaagcg uaggcuggcc agagggucuu 5340
cccccucuuu ggccagcucu ucagcuaguc aguugucugc gcccucauug aaggcgacau 5400
gcaccaccca ucaugacucc ccagacgcug accucauuga ggccaaccuc cuguggcggc 5460
aggagauggg agggaacauc acccgugugg agucagagaa caagguggua auccuggacu 5520
cuuuugaccc gcuucgagcg gaggaggacg agagggaggu gucuguugcg gcggagaucc 5580
ugcggaaaac caggaaguuc cccccagcga ugcccauaug ggcacgcccg gacuacaacc 5640
caccgcugcu agagacuugg aaggacccgg acuacguccc uccaguggug cacgggugcc 5700
cauugccacc uaccaagacc ccuccaauac caccuccgcg gaggaaaaag acaguugucc 5760
ugacagaguc caccgugucu ucugcccugg cggagcuugc cacaaagacc uuuggcagcu 5820
ccggaucguc ggccgucgac agcggcacag cgaccgcccc cccuaaccag cucuccgacg 5880
aaguggauac aggauccgac guugagucgu acuccuccau gcccccccuu gagggagagc 5940
cgggggaccc cgaucucagc gacgggucuu ggucuacugu aagugaggag gcuggugagg 6000
acgucgucug cugcucgaug uccuacacau ggacaggcgc cuugaucacg ccgugcgccg 6060
cggaggagag caagcugccc aucaaugcgc ugagcaacuc uuugcugcgc caccacaaca 6120
uggucuaugc cacaacaucc cgcagcgcaa gccaacggca gaaaaagguc accuuugaca 6180
gacugcaagu ccuggacgac cauuaccggg acgugcucaa ggagaugaag gcgaaggcgu 6240
ccacaguuaa ggcuaaacuu cuauccguag aagaggccug caagcugacg cccccacacu 6300
cagccagguc caaauuuggc uauggggcga aggacguccg gaaccuaucc agcaaggccg 6360
uuaaccacau caacuccgug uggaaggacu ugcuggaaga cacugagaca ccaauugaca 6420
ccaccaucau ggcaaaaaau gaggucuucu guguucaacc agagaaggga ggccgcaagc 6480
cagcucgccu uaucguauac ccagacuugg gggugcgugu gugcgagaaa auggcccuuu 6540
acgacguggu cuccacucuu ccucaggccg ugaugggcuc cucauacgga uuccaguacu 6600
cuccugggca gcgggucgag uuccugguga augccuggaa aucaaagaag aacccuaugg 6660
gcuucgcaua ugacacccgc uguuuugacu caacggucac cgagaacgac auccguguug 6720
aggagucaau uuaccaaugu ugugacuugg cccccgaggc cagacaggug auaaggucgc 6780
ucacagagcg gcuuuauguc gggggccccc ugacuaauuc aaaagggcag aacugcgguu 6840
aucgccggug ccgcgccagc ggcgugcuga cgacuagcug cgguaauacc cucacauguu 6900
acuugaaggc cucugcagcc ugucgagcug caaagcucca ggacugcacg augcucgugu 6960
gcggggacga ccuugucguu aucugugaaa gcgcggggac ccaggaggac gcggcgagcc 7020
uacgagucuu cacggaggcu augacuaggu acuccgcccc ccccggggac ccgccccgac 7080
cggaauacga cuuggaguug auaacaucau gcuccuccaa cgugucgguc gcgcacgaug 7140
caucuggcaa acggguguau uaccucaccc gugaccccac caccccccuu gcgcgggcug 7200
cgugggagac agcuaaacac acuccaguca acuccuggcu aggcaacauc aucauguaug 7260
cgcccacccu cugggcaagg augauucuga ugacucacuu cuucuccauc cuucuagcuc 7320
aggagcagcu ugaaaaagcc cuggauuguc agaucuacgg ggccacuuac uccauugaac 7380
cacuugaccu accucagauc auucaacgac uccauggucu uagcgcauuc ucacuccaua 7440
guuacucucc aggugaaauc aauagggugg cuucaugccu caggaaacuu gggguaccgc 7500
ccuugcgagu cuggagacau cgggccagaa guguccgcgc uaagcuacug ucccaggggg 7560
ggagggcugc cacuuguggc aaguaccucu ucaacugggc aguaaggacc aagcucaaac 7620
ucacuccaau cccggcugcg ucccaguugg acuuguccgg cugguucauu gcugguuaca 7680
gcgggggaga cauauaucac agccugucuc gugcccgacc ccgcugguuu auguugugcc 7740
uacuccuacu uucugugggg guaggcaucu accugcuccc caaucgauga acggggggcu 7800
aaacacucca ggccaauagg ccauucuguu uuuuuuuuuu uuuuuuuuuu uuuuuuuuuu 7860
uuuuuuuuuu uuuuuuuuuu uuccuuuuuu uuuuuuuuuu ucccuuucuu uugguggcuc 7920
caucuuagcc cuagucacgg cuagcuguga aagguccgug agccgcauga cugcagagag 7980
ugcugauacu ggccucucug cagaucaugu 8010
<210>10
<211>9594
<212>RNA
<213>丙型肝炎病毒
<400>10
gccagccccc ugaugggggc gacacuccac cauagaucac uccccuguga ggaacuacug 60
ucuucacgca gaaagcgucu agccauggcg uuaguaugag ugucgugcag ccuccaggac 120
ccccccuccc gggagagcca uaguggucug cggaaccggu gaguacaccg gaauugccag 180
gacgaccggg uccuuucuug gaucaacccg cucaaugccu ggagauuugg gcgugccccc 240
gcgagacugc uagccgagua guguuggguc gcgaaaggcc uugugguacu gccugauagg 300
gugcuugcga gugccccggg aggucucgua gaccgugcau caugagcaca aauccuaaac 360
cucaaagaaa aaccaaacgu aacaccaacc gccgcccaca ggacgucaag uucccgggcg 420
guggucagau cguuggugga guuuaccugu ugccgcgcag gggccccagg uugggugugc 480
gcgcgacuag gaagacuucc gagcggucgc aaccucguga aaggcggcaa ccuaucccca 540
aggcucgccg ccccgagggc agggccuggg cucagcccgg guacccuugg ccccucuaug 600
gcaaugaggg ucuggggugg gcaggguggc uccugucacc ccgcggcucc cggccuaauu 660
ggggccccac ggacccccgg cguaggucgc guaauuuggg uaaggucauc gauacccuca 720
caugcggcuu cgccgaccuc augggguaca uuccgcucgu cggcgccccc cuaggaggcg 780
uugccagggc ccuggcgcau ggcguccggg uucuggagga cggcgugaac uaugcaacag 840
ggaauuugcc cgguugcucu uucucuaucu uccucuuggc uuugcugucc uguuugacug 900
ucccagcuuc cgcuuaugaa gugcgcaacg uguccgggac auaccauguc acgaacgacu 960
gcgccaacuc aagcauugug uaugaggcag cggacauaau caugcacacc ccugggugcg 1020
ugcccugcgu ccgggagggc aauuccuccc gcugcugggu agcgcucacu cccacgcucg 1080
cggccaggaa caggagcauc cccacuacga cgauacgacg ccacgucgau uugcucguug 1140
gggcggcugc cuucugcucc gccauguacg ugggggaucu cugcgggucu guuuuccuag 1200
ucucccaacu guucaccuuc ucaccucgcc gguaugagac gguacaagaa ugcaauugcu 1260
caaucuaucc cggccacgua ucaggucacc gcauggcuug ggauaugaug augaauuggu 1320
cgcccacagc agcucuagug gugucacagu uacuccgaau cccacaagcc gucguggaua 1380
ugguggcagg ggcccacugg gggguucugg cgggucuugc cuacuauucc auggugggga 1440
acugggcuaa agucuugauu gugaugcuac ucuuugccgg cguugacggg accaccaccg 1500
ugacaggggg agcggcggcc uuuggcacca ggagccuugc guccuucuuu acauuagggc 1560
cgucucagaa aauccaacuu guaaacacca acggcaguug gcacaucaau aggacugccu 1620
ugaauuguaa ugacucccuc cagacugggu uccuugcugc gcuguucuau gcacacaaga 1680
ucaacacguc uggaugccca gagcgcaugg ccagcugccg cccuauugac aaguucgcuc 1740
aggggugggg ucccaucacc cauggugcgc cugacaccuc ggaccagagg cccuacugcu 1800
ggcacuacgc accucgaccg ugugguaucg uacccgcguc ggaggugugu ggcccagugu 1860
auuguuucac cccaagcccu guaguggugg ggacgaccga ucgcuucggc guccccacgu 1920
auagcugggg ggagaauaag acggacgugc ugcuccucaa caacacgcgg ccgccgcagg 1980
gcaauugguu cggcugcaca uggaugaaug gcaccggguu caccaagacg ugugggggcc 2040
ccccguguga uaucgggggg gucggcaaca acaccuugac cugccccacg gauugcuucc 2100
ggaagcaccc cgaggccacu uauaccaaau gcggcucggg gccuugguug acgccuaggu 2160
gucuaguuga cuacccauac aggcuuuggc acuaccccug cacugucaac uuuaccaucu 2220
ucaaggucag gauguaugug gggggcgugg agcacaggcu caacgcugcg ugcaacugga 2280
cucgaggaga gcgcugugac cuagaggaca gggacagauc agagcuuagc ccgcugcuac 2340
ugucuacaac agaguggcag auacugcccu guuccuucac cacccuaccg gcucugucca 2400
cuggcuugau ccaccuccau cagaacaucg uggacgugca auaccuguac gguguagggu 2460
cagcaguugu cuccguugug aucagauggg aguacguccu gcugcucuuc cuccuccugg 2520
cggacgcgcg cguuugugcc ugcuuaugga ugaugcuguu gauagcccag gcugaagccg 2580
ccuuggagaa ccugguaguc cucaacgcgg cguccguggc cggagcgcau ggcauccucu 2640
cuuuccuugu guucuucugc gcugccuggu acaucaaagg caagcuagug ccuggggugg 2700
cguaugcucu cuauggugua uggccgcugc uccugcuccu gcuggcguug ccacaacggg 2760
cguacgccau ggaccgggag auggcugcau cgugcggagg cgcgguuuuc gugggucugg 2820
uacucuugac cuugucacca cacuauaaag cauuccuugc caaguccaua uggugguuac 2880
aauauuuaau caccagggcc gaggcgcauu ugcaagugug gguccccccc cucaacguuc 2940
gggggggccg cgaugccauc auccuccuca cgugcgcggu ccacccagag cuaauuuuug 3000
acaucaccaa aauuuugcuc gccauauuug gcccgcucau ggugcuccag gcuggucuaa 3060
cuagagugcc guacuuugug cgcgcucaag ggcucauccg ugugugcaug uuggugcgga 3120
aagucgcugg gggucauuau auccaaaugg cucucaugag guuggccgca cugacgggca 3180
cguacguuua ugaucaucuu acuccgcugc gggacugggc ccaugcgggc uugcgagacc 3240
uugcgguggc aguugagccc gucguuuucu ccaacacaga gaccaagauu aucaccuggg 3300
gggcggacac cgcggcgugu ggggacauca ucuugggucu accugucucc gcccgaaggg 3360
ggagagaggu acuccuagga ccggccgaua acuuuggaga gcaagggugg cgacuccuug 3420
cgcccaucac ggccuacucc caacagacgc ggggcuuacu uggcuguauc aucaccggcc 3480
ucacaggucg agacaagaac caggucgaag gggagguuca ggugguuucc accgcaacac 3540
agucuuucuu ggcaaccugc gucaacggug uguguuggac ugucuaccau ggugccggcu 3600
caaagacccu agccggcccg aaggggccaa ucacccagau guacaccaac guagaccaag 3660
accucguugg cuggcaggcg ccccccgggg cgcguuccau gacgccgugc accugcggca 3720
gcucggaccu uuacuugguc acgaggcaug cugaugucau uccggugcgc cggcggggug 3780
acagcagagg gagccuacuu ucccccaggc ccgucuccua cuugaagggc ucuucaggug 3840
guccacugcu cugccccuug gggcacgucg ugggcaucuu ucgggcugcc gugugcaccc 3900
gggggguugc gaaggcggug gacuucauac ccaucgaguc uauggaaacu accaugcggu 3960
cuccggucuu uacggauaau ucaucucccc cggccguacc gcagacuuuu caaguggccc 4020
aucugcacgc ccccacuggc agcggcaaga gcaccaaggu gccagcugcg uaugcagccc 4080
agggguacaa ggugcuuguc uugaauccau ccguugccgc caccuugggu uuuggggcgu 4140
auauguccaa ggcauacggu gucgacccua acauuagaac ugggguaagg accaucacca 4200
caggcgcucc caucacguac uccaccuacg gcaaguuccu ugccgacggu gguugcuccg 4260
ggggcgcuua cgacaucaua auaugcgaug agugccacuc aaccgacucg acuuccauuu 4320
ugggcauugg cacgguccug gaucaagcgg agacggcugg agcgcgacuc gucgugcucg 4380
ccaccgcuac gccuccggga ucggucacug ugccacaccc caacaucgag gagguggccu 4440
uguccaacac cggagagauu cccuucuaug gcaaagccau cccccucgag gucaucaagg 4500
gggggaggca ucucauuuuc ugucauucua agaagaagug ugaugagcuc gcugcaaagc 4560
ugucgggccu uggggucaac gcuguagcgu acuaccgggg ucuugaugug uccgucauac 4620
caacaagcgg ggacgucguu gucguggcaa cagacgcucu aaugacgggc uacaccggug 4680
acuuugacuc ugugaucgac uguaauacau gugucaccca gacagucgac uucagccugg 4740
accccaccuu caccauugag acgacgaccg ugccccaaga cgcagugucg cgcucgcagc 4800
ggcgagggag gacugguagg gguagagggg gcauauacag guuugugacu ccaggagagc 4860
ggcccucggg cauguucgau uccucggucc ugugugaaug cuaugacgcg ggcugugcuu 4920
gguacgagcu cacgcccgcc gagaccucgg uuaggcugcg ggcuuaccua aauacaccag 4980
gguugcccgu cugccaggac cauuuggagu ucugggaagg cgucuucaca ggccucacuc 5040
auauagaugc ccacuucuug ucucagacua agcaggcagg agacaacuuc cccuaccugg 5100
uggcauacca ggccacagug ugcgccaggg cccaggcacc accuccauca ugggaucaaa 5160
uguggaagug ucucauacgg cuaaaaccua cacuacacgg gccaacaccc cuguuguaca 5220
ggcuaggagc cguccaaaac gaggucaccc ucacacaccc caugaccaaa uacaucauga 5280
caugcauguc ggcugaccua gaggucguca ccagcacuug ggugcuggug ggcggggucc 5340
ucgcagcuuu ggccgcguac ugcuugacaa cgggcagcgu gguuaucaua ggcaggauca 5400
ucuuguccgg aaggccggcu aucauucccg auagggaagu ucucuaccag gaguucgaug 5460
aaauggaaga gugcgccuca caccuucccu acaucgaaca aggaaugcag cucgccgagc 5520
aauucaagca gaaggcgcuc ggguuguugc aaacggccac caagcaagcg gaggccgcug 5580
cucccguggu ggaguccaaa uggcaagccc uugaggccuu cugggcgaag cacaugugga 5640
acuucaucag cgggauacag uaucuagcag gcuuguccac ucugccugga aaccccgcga 5700
uagcaucgcu gauggcauuu acagccucua ucacuagccc gcucaccacc caacauaccc 5760
uucuauuuaa caucuugggg ggaugggugg ccgcccaacu cgcccccccc agcgcugcuu 5820
cagccuucgu aggcgccggc aucgccggcg cggcuguugg cagcauaggu cuugggaagg 5880
ugcucgugga cauccuagcg gguuauggag cagggguggc aggcgcacuc guggccuuca 5940
aggucaugag cggcgaagug cccuccacug aggaccuggu caacuuacuc ccugccaucc 6000
ucuccccugg ugcccugguc gucggggucg ugugcgcagc gauacugcgu cggcaugugg 6060
gcccagggga gggggccgug caguggauga accggcugau agcguucgcu ucgcggggua 6120
accacgucuc ccccacgcac uaugugccug agagcgacgc cgcagcgcgu gucacccaga 6180
uccucuccag ccuuaccauc acucagcugc uaaagaggcu ccaccagugg auuaaugagg 6240
acuguuccac gccaugcucc gguucguggc ucagggaugu uugggacugg auaugcacgg 6300
uuuugaccga cuucaaaacc uggcuccagu ccaagcuccu gccacgguug ccgggacucc 6360
cuuucuuuuc augucaacgu ggauauaaag gagucuggcu gggagauggc guuaugcaaa 6420
cuaccugucc auguggugca caaaucagcg gacaugucaa aaacggcucc augaagaucg 6480
uggggccuaa aaccugcagc aacacguggc acgggacguu ccccaucaac gcauacacca 6540
caggccccug cacacccucc ccggcgccga acuauuccaa ggcguugugg cgaguggcug 6600
cugaggagua uguggagguc acgcgggugg gggauuucca cuacgugacg ggcaugacca 6660
cugacaacgu aaaaugccca ugccaggucc cggcccccga auucuucacg gaguuggaug 6720
gggugcggcu gcacagguac gcuccggcgu gcaagccucu cuuacgggau gaggucacau 6780
uccaggucgg gcucaaccag uauccgguug gaucacagcu uccaugugag cccgagccgg 6840
auguaacagu gcucacuucc augcucaccg accccuccca uauuacagca gagacggcua 6900
agcguaggcu ggccagaggg uccccccccu cuuuggccag cuccucagcu agccaguugu 6960
cugcgccuuc cuugaaggcg acaugcacua cccaccauga cuccccagau gcugaccuca 7020
ucgaggccaa ccuccugugg cggcaggaga ugggcgggaa caucacccgc guggagucag 7080
agaacaaggu aguaauucug gacucuuuug aaccgcuucg agcggaggag gaugauaggg 7140
aaguguccgu agcggcggag auccugcgga gaaccaggaa auuccccgca gcgaugccca 7200
uaugggcacg gccggacuac aacccaccac uccuagaguc uuggaagaac ccagacuacg 7260
ucccuccagu gguacacggg ugcccauuac caccuauuaa ggccccuccg auaccaccuc 7320
cacggagaaa gaggacgguc auccugacag aauccaccgu gucuucugcc uuggcggagc 7380
uugcuacaaa gaccuuuggc agcuccggau cgucggccgu ugacagcggc acagcgacug 7440
gcccuccuga ucaguccucc ggugacggag auacaggauc cgacgcugag ucgugcuccu 7500
ccaugccccc ccuugagggg gagccggggg accccgaucu cagcgacggg ucuuggucua 7560
ccgugagcga ggaggccggu gaggacgucg ucugcugcuc gauguccuac acauggacag 7620
gcgccuuaau cacaccgugc gccgcagagg agagcaagcu gccuaucaac gcguugagca 7680
acucuuugcu gcgccaccac aacauggucu augccacaac aucccgcagc gcgggccaac 7740
ggcagaagaa ggucacuuuu gacagagugc agguccugga cgaccauuac cgggacgugc 7800
ucaaggagau gaaggcgaag gcguccacag uuaaggcuaa acuucuaccu guagaagaag 7860
ccugcaggcu gacgccccca cacucggcca gauccaaguu uggcuauggg gcgaaggacg 7920
uccggaaccu auccagcaag gccgucaacc acauccacuc cguguggaag gacuugcugg 7980
aagacucuga gacgccgauu gacaccacca ucauggcaaa aaaugagguc uuuuguguuc 8040
aaccagagaa aggaggccgc aagucagcuc gucuuaucgu auucccagac uuggggguuc 8100
gugugugcga gaaaauggcc cuuuacgacg ugguuuccac ucuuccucag gccgugaugg 8160
gcuccucaua cggguuccag uacucuccug gacagcgggu cgaguuccug gugaaugccu 8220
ggaaaucaaa gaagaacccu augggcuucg cauaugacac ccgcuguuuu gacucaacgg 8280
ucacugagag ugacauccgu guugaggagu caauuuacca auguugugac uuggcccccg 8340
aggccagaca ggucauaagg ucgcucacgg agcggcuuua uaucgggggc ccccugacua 8400
auucaaaagg gcagagcugc ggcuaucgcc ggugccgcgc cagcggugug cugacgacca 8460
gcugcgguaa uacccucaca uguuacuuga aggcuucugc agccugucga gcugcaaagc 8520
uccaggacug cacaauguua gugugcggag acgaccuugu cguuaucugu gaaagugcgg 8580
gaacccagga ggacgcggcg agccuacgag ucuucacgga ggcuaugacu agguacucug 8640
ccccccccgg ggacccgccc cagccagaau acgacuugga gcugauaaca ucaugcuccu 8700
ccaacgucuc ggucgcgcac gaugcacuug gcaagcgggu guauuaucug acccgcgacc 8760
ccaccacccc ccuugcgcgg gcugcguggg agacagcaag acacacucca guuaacuccu 8820
ggcuaggcaa caucaucaug uaugcgccca cccuaugggc aaggaugauu cugaugaccc 8880
acuucuuuuc cauccuucua gcucaggaac aacuugaaaa agcccuagau ugucagaucu 8940
acggggccac uuacuccauu gagccacuug accuaccuca gaucauucag cgacuccacg 9000
gccuuagcgc auuuucacuc cauagcuacu cuccagguga gaucaauagg guggcuucau 9060
gccucaggaa acuuggggua ccacccuugc gagucuggag acaucgggcc agaagugucc 9120
gcgcuaagcu acugucccag ggggggaggg ccgccacuug uggcaaauac cucuucaacu 9180
gggcaguaag gaccaagcuc aaacucacuc caauuccggc ugcgucccag uuggacuugu 9240
ccggcugguu cauugcuggu uacagcgggg gagacauaua ucacagccug ucucgcgccc 9300
gaccccgcug guucaugugg ugccuacucc uacuuuccgu agggguaggc aucuaucugc 9360
uccccaaucg augaacgggg ggcuaaacac uccaggccaa uaggccauuc uguuuuuuuu 9420
uuuuuuuuuu uuuuuuuuuu uuuuuuuuuu uuuuuuuuuu uuuuuuccuu uuuuuuuuuu 9480
uuuuucccuu ucuuuuggug gcuccaucuu agcccuaguc acggcuagcu gugaaagguc 9540
cgugagccgc augacugcag agagugcuga uacuggccuc ucugcagauc augu 9594
<210>11
<211>3010
<212>PRT
<213>丙型肝炎病毒
<400>11
Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Thr Lys Arg Asn Thr Asn
1 5 10 15
Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gly Gly Gln Ile Val Gly
20 25 30
Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Arg Leu Gly Val Arg Ala
35 40 45
Thr Arg Lys Thr Ser Glu Arg Ser Gln Pro Arg Glu Arg Arg Gln Pro
50 55 60
Ile Pro Lys Ala Arg Arg Pro Glu Gly Arg Ala Trp Ala Gln Pro Gly
65 70 75 80
Tyr Pro Trp Pro Leu Tyr Gly Asn Glu Gly Leu Gly Trp Ala Gly Trp
85 90 95
Leu Leu Ser Pro Arg Gly Ser Arg Pro Asn Trp Gly Pro Thr Asp Pro
100 105 110
Arg Arg Arg Ser Arg Asn Leu Gly Lys Val Ile Asp Thr Leu Thr Cys
115 120 125
Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Leu Val Gly Ala Pro Leu
130 135 140
Gly Gly Val Ala Arg Ala Leu Ala His Gly Val Arg Val Leu Glu Asp
145 150 155 160
Gly Val Asn Tyr Ala Thr Gly Asn Leu Pro Gly Cys Ser Phe Ser Ile
165 170 175
Phe Leu Leu Ala Leu Leu Ser Cys Leu Thr Val Pro Ala Ser Ala Tyr
180 185 190
Glu Val Arg Asn Val Ser Gly Thr Tyr His Val Thr Asn Asp Cys Ala
195 200 205
Asn Ser Ser Ile Val Tyr Glu Ala Ala Asp Ile Ile Met His Thr Pro
210 215 220
Gly Cys Val Pro Cys Val Arg Glu Gly Asn Ser Ser Arg Cys Trp Val
225 230 235 240
Ala Leu Thr Pro Thr Leu Ala Ala Arg Asn Arg Ser Ile Pro Thr Thr
245 250 255
Thr Ile Arg Arg His Val Asp Leu Leu Val Gly Ala Ala Ala Phe Cys
260 265 270
Ser Ala Met Tyr Val Gly Asp Leu Cys Gly Ser Val Phe Leu Val Ser
275 280 285
Gln Leu Phe Thr Phe Ser Pro Arg Arg Tyr Glu Thr Val Gln Glu Cys
290 295 300
Asn Cys Ser Ile Tyr Pro Gly His Val Ser Gly His Arg Met Ala Trp
305 310 315 320
Asp Met Met Met Asn Trp Ser Pro Thr Ala Ala Leu Val Val Ser Gln
325 330 335
Leu Leu Arg Ile Pro Gln Ala Val Val Asp Met Val Ala Gly Ala His
340 345 350
Trp Gly Val Leu Ala Gly Leu Ala Tyr Tyr Ser Met Val Gly Asn Trp
355 360 365
Ala Lys Val Leu Ile Val Met Leu Leu Phe Ala Gly Val Asp Gly Thr
370 375 380
Thr Thr Val Thr Gly Gly Ala Ala Ala Phe Gly Thr Arg Ser Leu Ala
385 390 395 400
Ser Phe Phe Thr Leu Gly Pro Ser Gln Lys Ile Gln Leu Val Asn Thr
405 410 415
Asn Gly Ser Trp His Ile Asn Arg Thr Ala Leu Asn Cys Asn Asp Ser
420 425 430
Leu Gln Thr Gly Phe Leu Ala Ala Leu Phe Tyr Ala His Lys Ile Asn
435 440 445
Thr Ser Gly Cys Pro Glu Arg Met Ala Ser Cys Arg Pro Ile Asp Lys
450 455 460
Phe Ala Gln Gly Trp Gly Pro Ile Thr His Gly Ala Pro Asp Thr Ser
465 470 475 480
Asp Gln Arg Pro Tyr Cys Trp His Tyr Ala Pro Arg Pro Cys Gly Ile
485 490 495
Val Pro Ala Ser Glu Val Cys Gly Pro Val Tyr Cys Phe Thr Pro Ser
500 505 510
Pro Val Val Val Gly Thr Thr Asp Arg Phe Gly Val Pro Thr Tyr Ser
515 520 525
Trp Gly Glu Asn Lys Thr Asp Val Leu Leu Leu Asn Asn Thr Arg Pro
530 535 540
Pro Gln Gly Asn Trp Phe Gly Cys Thr Trp Met Asn Gly Thr Gly Phe
545 550 555 560
Thr Lys Thr Cys Gly Gly Pro Pro Cys Asp Ile Gly Gly Val Gly Asn
565 570 575
Asn Thr Leu Thr Cys Pro Thr Asp Cys Phe Arg Lys His Pro Glu Ala
580 585 590
Thr Tyr Thr Lys Cys Gly Ser Gly Pro Trp Leu Thr Pro Arg Cys Leu
595 600 605
Val Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe
610 615 620
Thr Ile Phe Lys Val Arg Met Tyr Val Gly Gly Val Glu His Arg Leu
625 630 635 640
Asn Ala Ala Cys Asn Trp Thr Arg Gly Glu Arg Cys Asp Leu Glu Asp
645 650 655
Arg Asp Arg Ser Glu Leu Ser Pro Leu Leu Leu Ser Thr Thr Glu Trp
660 665 670
Gln Ile Leu Pro Cys Ser Phe Thr Thr Leu Pro Ala Leu Ser Thr Gly
675 680 685
Leu Ile His Leu His Gln Asn Ile Val Asp Val Gln Tyr Leu Tyr Gly
690 695 700
Val Gly Ser Ala Val Val Ser Val Val Ile Arg Trp Glu Tyr Val Leu
705 710 715 720
Leu Leu Phe Leu Leu Leu Ala Asp Ala Arg Val Cys Ala Cys Leu Trp
725 730 735
Met Met Leu Leu Ile Ala Gln Ala Glu Ala Ala Leu Glu Asn Leu Val
740 745 750
Val Leu Asn Ala Ala Ser Val Ala Gly Ala His Gly Ile Leu Ser Phe
755 760 765
Leu Val Phe Phe Cys Ala Ala Trp Tyr Ile Lys Gly Lys Leu Val Pro
770 775 780
Gly Val Ala Tyr Ala Leu Tyr Gly Val Trp Pro Leu Leu Leu Leu Leu
785 790 795 800
Leu Ala Leu Pro Gln Arg Ala Tyr Ala Met Asp Arg Glu Met Ala Ala
805 810 815
Ser Cys Gly Gly Ala Val Phe Val Gly Leu Val Leu Leu Thr Leu Ser
820 825 830
Pro His Tyr Lys Ala Phe Leu Ala Lys Ser Ile Trp Trp Leu Gln Tyr
835 840 845
Leu Ile Thr Arg Ala Glu Ala His Leu Gln Val Trp Val Pro Pro Leu
850 855 860
Asn Val Arg Gly Gly Arg Asp Ala Ile Ile Leu Leu Thr Cys Ala Val
865 870 875 880
His Pro Glu Leu Ile Phe Asp Ile Thr Lys Ile Leu Leu Ala Ile Phe
885 890 895
Gly Pro Leu Met Val Leu Gln Ala Gly Leu Thr Arg Val Pro Tyr Phe
900 905 910
Val Arg Ala Gln Gly Leu Ile Arg Val Cys Met Leu Val Arg Lys Val
915 920 925
Ala Gly Gly His Tyr Ile Gln Met Ala Leu Met Arg Leu Ala Ala Leu
930 935 940
Thr Gly Thr Tyr Val Tyr Asp His Leu Thr Pro Leu Arg Asp Trp Ala
945 950 955 960
His Ala Gly Leu Arg Asp Leu Ala Val Ala Val Glu Pro Val Val Phe
965 970 975
Ser Asn Thr Glu Thr Lys Ile Ile Thr Trp Gly Ala Asp Thr Ala Ala
980 985 990
Cys Gly Asp Ile Ile Leu Gly Leu Pro Val Ser Ala Arg Arg Gly Arg
995 1000 1005
Glu Val Leu Leu Gly Pro Ala Asp Asn Phe Gly Glu Gln Gly Trp
1010 1015 1020
Arg Leu Leu Ala Pro Ile Thr Ala Tyr Ser Gln Gln Thr Arg Gly
1025 1030 1035
Leu Leu Gly Cys Ile Ile Thr Gly Leu Thr Gly Arg Asp Lys Asn
1040 1045 1050
Gln Val Glu Gly Glu Val Gln Val Val Ser Thr Ala Thr Gln Ser
1055 1060 1065
Phe Leu Ala Thr Cys Val Asn Gly Val Cys Trp Thr Val Tyr His
1070 1075 1080
Gly Ala Gly Ser Lys Thr Leu Ala Gly Pro Lys Gly Pro Ile Thr
1085 1090 1095
Gln Met Tyr Thr Asn Val Asp Gln Asp Leu Val Gly Trp Gln Ala
1100 1105 1110
Pro Pro Gly Ala Arg Ser Met Thr Pro Cys Thr Cys Gly Ser Ser
1115 11201125
Asp Leu Tyr Leu Val Thr Arg His Ala Asp Val Ile Pro Val Arg
1130 1135 1140
Arg Arg Gly Asp Ser Arg Gly Ser Leu Leu Ser Pro Arg Pro Val
1145 1150 1155
Ser Tyr Leu Lys Gly Ser Ser Gly Gly Pro Leu Leu Cys Pro Leu
1160 1165 1170
Gly His Val Val Gly Ile Phe Arg Ala Ala Val Cys Thr Arg Gly
1175 1180 1185
Val Ala Lys Ala Val Asp Phe Ile Pro Ile Glu Ser Met Glu Thr
1190 1195 1200
Thr Met Arg Ser Pro Val Phe Thr Asp Asn Ser Ser Pro Pro Ala
1205 1210 1215
Val Pro Gln Thr Phe Gln Val Ala His Leu His Ala Pro Thr Gly
1220 1225 1230
Ser Gly Lys Ser Thr Lys Val Pro Ala Ala Tyr Ala Ala Gln Gly
1235 1240 1245
Tyr Lys Val Leu Val Leu Asn Pro Ser Val Ala Ala Thr Leu Gly
1250 1255 1260
Phe Gly Ala Tyr Met Ser Lys Ala Tyr Gly Val Asp Pro Asn Ile
1265 1270 1275
Arg Thr Gly Val Arg Thr Ile Thr Thr Gly Ala Pro Ile Thr Tyr
1280 1285 1290
Ser Thr Tyr Gly Lys Phe Leu Ala Asp Gly Gly Cys Ser Gly Gly
1295 1300 1305
Ala Tyr Asp Ile Ile Ile Cys Asp Glu Cys His Ser Thr Asp Ser
1310 1315 1320
Thr Ser Ile Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr
1325 1330 1335
Ala Gly Ala Arg Leu Val Val Leu Ala Thr Ala Thr Pro Pro Gly
1340 1345 1350
Ser Val Thr Val Pro His Pro Asn Ile Glu Glu Val Ala Leu Ser
1355 1360 1365
Asn Thr Gly Glu Ile Pro Phe Tyr Gly Lys Ala Ile Pro Leu Glu
1370 1375 1380
Val Ile Lys Gly Gly Arg His Leu Ile Phe Cys His Ser Lys Lys
1385 1390 1395
Lys Cys Asp Glu Leu Ala Ala Lys Leu Ser Gly Leu Gly Val Asn
1400 1405 14l0
Ala Val Ala Tyr Tyr Arg Gly Leu Asp Val Ser Val Ile Pro Thr
1415 1420 1425
Ser Gly Asp Val Val Val Val Ala Thr Asp Ala Leu Met Thr Gly
1430 1435 1440
Tyr Thr Gly Asp Phe Asp Ser Val Ile Asp Cys Asn Thr Cys Val
1445 1450 1455
Thr Gln Thr Val Asp Phe Ser Leu Asp Pro Thr Phe Thr Ile Glu
1460 1465 1470
Thr Thr Thr Val Pro Gln Asp Ala Val Ser Arg Ser Gln Arg Arg
1475 1480 1485
Gly Arg Thr Gly Arg Gly Arg Gly Gly Ile Tyr Arg Phe Val Thr
1490 1495 1500
Pro Gly Glu Arg Pro Ser Gly Met Phe Asp Ser Ser Val Leu Cys
1505 1510 1515
Glu Cys Tyr Asp Ala Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala
1520 1525 1530
Glu Thr Ser Val Arg Leu Arg Ala Tyr Leu Asn Thr Pro Gly Leu
1535 1540 1545
Pro Val Cys Gln Asp His Leu Glu Phe Trp Glu Gly Val Phe Thr
1550 1555 1560
Gly Leu Thr His Ile Asp Ala His Phe Leu Ser Gln Thr Lys Gln
1565 1570 1575
Ala Gly Asp Asn Phe Pro Tyr Leu Val Ala Tyr Gln Ala Thr Val
1580 1585 1590
Cys Ala Arg Ala Gln Ala Pro Pro Pro Ser Trp Asp Gln Met Trp
1595 1600 1605
Lys Cys Leu Ile Arg Leu Lys Pro Thr Leu His Gly Pro Thr Pro
1610 1615 1620
Leu Leu Tyr Arg Leu Gly Ala Val Gln Asn Glu Val Thr Leu Thr
1625 1630 1635
His Pro Met Thr Lys Tyr Ile Met Thr Cys Met Ser Ala Asp Leu
1640 1645 1650
Glu Val Val Thr Ser Thr Trp Val Leu Val Gly Gly Val Leu Ala
1655 1660 1665
Ala Leu Ala Ala Tyr Cys Leu Thr Thr Gly Ser Val Val Ile Ile
1670 1675 1680
Gly Arg Ile Ile Leu Ser Gly Arg Pro Ala Ile Ile Pro Asp Arg
1685 1690 1695
Glu Val Leu Tyr Gln Glu Phe Asp Glu Met Glu Glu Cys Ala Ser
1700 1705 1710
His Leu Pro Tyr Ile Glu Gln Gly Met Gln Leu Ala Glu Gln Phe
1715 1720 1725
Lys Gln Lys Ala Leu Gly Leu Leu Gln Thr Ala Thr Lys Gln Ala
1730 1735 1740
Glu Ala Ala Ala Pro Val Val Glu Ser Lys Trp Gln Ala Leu Glu
1745 1750 1755
Ala Phe Trp Ala Lys His Met Trp Asn Phe Ile Ser Gly Ile Gln
1760 1765 1770
Tyr Leu Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Ile Ala
1775 1780 1785
Ser Leu Met Ala Phe Thr Ala Ser Ile Thr Ser Pro Leu Thr Thr
1790 1795 1800
Gln His Thr Leu Leu Phe Asn Ile Leu Gly Gly Trp Val Ala Ala
1805 1810 1815
Gln Leu Ala Pro Pro Ser Ala Ala Ser Ala Phe Val Gly Ala Gly
1820 1825 1830
Ile Ala Gly Ala Ala Val Gly Ser Ile Gly Leu Gly Lys Val Leu
1835 1840 1845
Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu
1850 1855 1860
Val Ala Phe Lys Val Met Ser Gly Glu Val Pro Ser Thr Glu Asp
1865 1870 1875
Leu Val Asn Leu Leu Pro Ala Ile Leu Ser Pro Gly Ala Leu Val
1880 1885 1890
Val Gly Val Val Cys Ala Ala Ile Leu Arg Arg His Val Gly Pro
1895 1900 1905
Gly Glu Gly Ala Val Gln Trp Met Asn Arg Leu Ile Ala Phe Ala
1910 1915 1920
Ser Arg Gly Asn His Val Ser Pro Thr His Tyr Val Pro Glu Ser
1925 1930 1935
Asp Ala Ala Ala Arg Val Thr Gln Ile Leu Ser Ser Leu Thr Ile
1940 1945 1950
Thr Gln Leu Leu Lys Arg Leu His Gln Trp Ile Asn Glu Asp Cys
1955 1960 1965
Ser Thr Pro Cys Ser Gly Ser Trp Leu Arg Asp Val Trp Asp Trp
1970 1975 1980
Ile Cys Thr Val Leu Thr Asp Phe Lys Thr Trp Leu Gln Ser Lys
1985 1990 1995
Leu Leu Pro Arg Leu Pro Gly Leu Pro Phe Phe Ser Cys Gln Arg
2000 2005 2010
Gly Tyr Lys Gly Val Trp Leu Gly Asp Gly Val Met Gln Thr Thr
2015 2020 2025
Cys Pro Cys Gly Ala Gln Ile Ser Gly His Val Lys Asn Gly Ser
2030 2035 2040
Met Lys Ile Val Gly Pro Lys Thr Cys Ser Asn Thr Trp His Gly
2045 2050 2055
Thr Phe Pro Ile Asn Ala Tyr Thr Thr Gly Pro Cys Thr Pro Ser
2060 2065 2070
Pro Ala Pro Asn Tyr Ser Lys Ala Leu Trp Arg Val Ala Ala Glu
2075 2080 2085
Glu Tyr Val Glu Val Thr Arg Val Gly Asp Phe His Tyr Val Thr
2090 2095 2100
Gly Met Thr Thr Asp Asn Val Lys Cys Pro Cys Gln Val Pro Ala
2105 2110 2115
Pro Glu Phe Phe Thr Glu Leu Asp Gly Val Arg Leu His Arg Tyr
2120 2125 2130
Ala Pro Ala Cys Lys Pro Leu Leu Arg Asp Glu Val Thr Phe Gln
2135 2140 2145
Val Gly Leu Asn Gln Tyr Pro Val Gly Ser Gln Leu Pro Cys Glu
2150 2155 2160
Pro Glu Pro Asp Val Thr Val Leu Thr Ser Met Leu Thr Asp Pro
2165 2170 2175
Ser His Ile Thr Ala Glu Thr Ala Lys Arg Arg Leu Ala Arg Gly
2180 2185 2190
Ser Pro Pro Ser Leu Ala Ser Ser Ser Ala Ser Gln Leu Ser Ala
2195 2200 2205
Pro Ser Leu Lys Ala Thr Cys Thr Thr His His Asp Ser Pro Asp
2210 2215 2220
Ala Asp Leu Ile Glu Ala Asn Leu Leu Trp Arg Gln Glu Met Gly
2225 2230 2235
Gly Asn Ile Thr Arg Val Glu Ser Glu Asn Lys Val Val Ile Leu
2240 2245 2250
Asp Ser Phe Glu Pro Leu Arg Ala Glu Glu Asp Asp Arg Glu Val
2255 2260 2265
Ser Val Ala Ala Glu Ile Leu Arg Arg Thr Arg Lys Phe Pro Ala
2270 2275 2280
Ala Met Pro Ile Trp Ala Arg Pro Asp Tyr Asn Pro Pro Leu Leu
2285 2290 2295
Glu Ser Trp Lys Asn Pro Asp Tyr Val Pro Pro Val Val His Gly
2300 2305 2310
Cys Pro Leu Pro Pro Ile Lys Ala Pro Pro Ile Pro Pro Pro Arg
2315 2320 2325
Arg Lys Arg Thr Val Ile Leu Thr Glu Ser Thr Val Ser Ser Ala
2330 2335 2340
Leu Ala Glu Leu Ala Thr Lys Thr Phe Gly Ser Ser Gly Ser Ser
2345 2350 2355
Ala Val Asp Ser Gly Thr Ala Thr Gly Pro Pro Asp Gln Ser Ser
2360 2365 2370
Gly Asp Gly Asp Thr Gly Ser Asp Ala Glu Ser Cys Ser Ser Met
2375 2380 2385
Pro Pro Leu Glu Gly Glu Pro Gly Asp Pro Asp Leu Ser Asp Gly
2390 2395 2400
Ser Trp Ser Thr Val Ser Glu Glu Ala Gly Glu Asp Val Val Cys
2405 2410 2415
Cys Ser Met Ser Tyr Thr Trp Thr Gly Ala Leu Ile Thr Pro Cys
2420 2425 2430
Ala Ala Glu Glu Ser Lys Leu Pro Ile Asn Ala Leu Ser Asn Ser
2435 2440 2445
Leu Leu Arg His His Asn Met Val Tyr Ala Thr Thr Ser Arg Ser
2450 2455 2460
Ala Gly Gln Arg Gln Lys Lys Val Thr Phe Asp Arg Val Gln Val
2465 2470 2475
Leu Asp Asp His Tyr Arg Asp Val Leu Lys Glu Met Lys Ala Lys
2480 2485 2490
Ala Ser Thr Val Lys Ala Lys Leu Leu Pro Val Glu Glu Ala Cys
2495 2500 2505
Arg Leu Thr Pro Pro His Ser Ala Arg Ser Lys Phe Gly Tyr Gly
2510 2515 2520
Ala Lys Asp Val Arg Asn Leu Ser Ser Lys Ala Val Asn His Ile
2525 2530 2535
His Ser Val Trp Lys Asp Leu Leu Glu Asp Ser Glu Thr Pro Ile
2540 2545 2550
Asp Thr Thr Ile Met Ala Lys Asn Glu Val Phe Cys Val Gln Pro
2555 2560 2565
Glu Lys Gly Gly Arg Lys Ser Ala Arg Leu Ile Val Phe Pro Asp
2570 2575 2580
Leu Gly Val Arg Val Cys Glu Lys Met Ala Leu Tyr Asp Val Val
2585 2590 2595
Ser Thr Leu Pro Gln Ala Val Met Gly Ser Ser Tyr Gly Phe Gln
2600 2605 2610
Tyr Ser Pro Gly Gln Arg Val Glu Phe Leu Val Asn Ala Trp Lys
26l5 2620 2625
Ser Lys Lys Asn Pro Met Gly Phe Ala Tyr Asp Thr Arg Cys Phe
2630 2635 2640
Asp Ser Thr Val Thr Glu Ser Asp Ile Arg Val Glu Glu Ser Ile
2645 2650 2655
Tyr Gln Cys Cys Asp Leu Ala Pro Glu Ala Arg Gln Val Ile Arg
2660 2665 2670
Ser Leu Thr Glu Arg Leu Tyr Ile Gly Gly Pro Leu Thr Asn Ser
2675 2680 2685
Lys Gly Gln Ser Cys Gly Tyr Arg Arg Cys Arg Ala Ser Gly Val
2690 2695 2700
Leu Thr Thr Ser Cys Gly Asn Thr Leu Thr Cys Tyr Leu Lys Ala
2705 2710 2715
Ser Ala Ala Cys Arg Ala Ala Lys Leu Gln Asp Cys Thr Met Leu
2720 2725 2730
Val Cys Gly Asp Asp Leu Val Val Ile Cys Glu Ser Ala Gly Thr
2735 2740 2745
Gln Glu Asp Ala Ala Ser Leu Arg Val Phe Thr Glu Ala Met Thr
2750 2755 2760
Arg Tyr Ser Ala Pro Pro Gly Asp Pro Pro Gln Pro Glu Tyr Asp
2765 2770 2775
Leu Glu Leu Ile Thr Ser Cys Ser Ser Asn Val Ser Val Ala His
2780 2785 2790
Asp Ala Leu Gly Lys Arg Val Tyr Tyr Leu Thr Arg Asp Pro Thr
2795 2800 2805
Thr Pro Leu Ala Arg Ala Ala Trp Glu Thr Ala Arg His Thr Pro
2810 2815 2820
Val Asn Ser Trp Leu Gly Asn Ile Ile Met Tyr Ala Pro Thr Leu
2825 2830 2835
Trp Ala Arg Met Ile Leu Met Thr His Phe Phe Ser Ile Leu Leu
2840 2845 2850
Ala Gln Glu Gln Leu Glu Lys Ala Leu Asp Cys Gln Ile Tyr Gly
2855 2860 2865
Ala Thr Tyr Ser Ile Glu Pro Leu Asp Leu Pro Gln Ile Ile Gln
2870 2875 2880
Arg Leu His Gly Leu Ser Ala Phe Ser Leu His Ser Tyr Ser Pro
2885 2890 2895
Gly Glu Ile Asn Arg Val Ala Ser Cys Leu Arg Lys Leu Gly Val
2900 2905 2910
Pro Pro Leu Arg Val Trp Arg His Arg Ala Arg Ser Val Arg Ala
2915 2920 2925
Lys Leu Leu Ser Gln Gly Gly Arg Ala Ala Thr Cys Gly Lys Tyr
2930 2935 2940
Leu Phe Asn Trp Ala Val Arg Thr Lys Leu Lys Leu Thr Pro Ile
2945 2950 2955
Pro Ala Ala Ser Gln Leu Asp Leu Ser Gly Trp Phe Ile Ala Gly
2960 2965 2970
Tyr Ser Gly Gly Asp Ile Tyr His Ser Leu Ser Arg Ala Arg Pro
2975 2980 2985
Arg Trp Phe Met Trp Cys Leu Leu Leu Leu Ser Val Gly Val Gly
2990 2995 3000
Ile Tyr Leu Leu Pro Asn Arg
3005 3010
<210>12
<211>30
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>12
tcatgcggct cacggacctt tcacagctag 30
<210>13
<211>30
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>13
atcgtcttca cgcagaaagc gtctagccat 30
<210>14
<211>26
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>14
gcctattggc ctggagtgtt tagctc 26
<210>15
<211>29
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>15
atggcgttag tatgagtgtc gtgcagcct 29
<210>16
<211>31
<212>DNA
<213>人工序列
<220>
<223>HcV的引物
<400>16
tcgggcacga gacaggctgt gatatatgtc t 31
<210>17
<211>19
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>17
tgcacggtct acgagacct 19
<210>18
<211>24
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>18
ctcgcaagca ccctatcagc cagt 24
<210>19
<211>19
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>19
aggcattgag cgggtttat 19
<210>20
<211>38
<212>DNA
<213>人工序列
<220>
<223>RACE的引物
<400>20
ctagactcga gtcgacatcg tttttttttt tttttttt 38
<210>21
<211>20
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>21
atcttagccc tagtcacggc 20
<210>22
<211>20
<212>DNA
<213>人工序列
<220>
<223>RACE的引物
<400>22
ctagactcga gtcgacatcg 20
<210>23
<211>29
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>23
ctagctgtaa aggtccgtga gccgcatga 29
<210>24
<211>17
<212>DNA
<213>人工序列
<220>
<223>引物
<400>24
gtaaaacgac ggccagt 17
<210>25
<211>17
<212>DNA
<213>人工序列
<220>
<223>引物
<400>25
caggaaacag ctatgac 17
<210>26
<211>20
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>26
aggaagactt ccgagcggtc 20
<210>27
<211>32
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>27
ggaacttgcc cggttgctct ttctctatct tc 32
<210>28
<211>25
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>28
attccatggt ggggaactgg gctaa 25
<210>29
<211>30
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>29
taacaatacc ttgacctgcc ccacggactg 30
<210>30
<211>29
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>30
aacatcgtgg acgtgcaata cctgtacgg 29
<210>31
<211>20
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>31
gaccctacac cgtacaggta 20
<210>32
<211>26
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>32
ttggaccggg agatggctgc atcgtg 26
<210>33
<211>21
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>33
cacccaaatg tacaccaatg t 21
<210>34
<211>22
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>34
tacccgttga gtctatggaa ac 22
<210>35
<211>20
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>35
cacttggaat gtctgcggta 20
<210>36
<211>25
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>36
agggggggag gcatctcatt ttctg 25
<210>37
<211>26
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>37
tgctatgacg cgggctgtgc ttggta 26
<210>38
<211>21
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>38
ggtcattgtg ggcaggatca t 21
<210>39
<211>20
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>39
ctgcctggaa accccgcgat 20
<210>40
<211>24
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>40
tggcagcata ggccttggga aggt 24
<210>41
<211>21
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>41
aagacctggc tccagtccaa g 21
<210>42
<211>21
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>42
ttccatgctc accgacccct c 21
<210>43
<211>20
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>43
accttattct ctgactccac 20
<210>44
<211>21
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>44
cagaagaagg tcacc tttga c 21
<210>45
<211>25
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>45
gcagcgggtc gagttcctgg tgaat 25
<210>46
<211>26
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>46
ctacggggcc tgttactcca ttgaac 26
<210>47
<211>26
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>47
cttgaaaaag ccctggattg tcagat 26
<210>48
<211>35
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>48
acatgatctg cagagaggcc agtatcagca ctctc 35
<210>49
<211>31
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>49
gccagccccc tgatgggggc gacactccac c 31
<210>50
<211>25
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>50
agccgcatgt aagggtatcg atgac 25
<210>51
<211>20
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>51
acatgatctg cagagaggcc 20
<210>52
<211>30
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>52
gagtacaccg gaattgccag gacgaccggg 30
<210>53
<211>25
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>53
attccatggt ggggaactgg gccaa 25
<210>54
<211>24
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>54
catccatgtg cagccgaacc aatt 24
<210>55
<211>30
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>55
aggggtagtg ccaaagcctg tatgggtagt 30
<210>56
<211>31
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>56
ataatgaccc ccggcgactt tccgcactaa c 31
<210>57
<211>20
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>57
catggtagac agtccagcac 20
<210>58
<211>24
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>58
gacatgcatg tcatgatgta tttg 24
<210>59
<211>20
<212>DNA
<213>人工序列
<220>
<223>HCV的引物
<400>59
ctcatgacct taaaggccac 20
<210>60
<211>30
<212>DNA
<213>人工序列
<220>
<223>ECMV IRES的引物
<400>60
tgcacatgct ctacatgtgt ttagtcgagg 30
<210>61
<211>9594
<212>RNA
<213>丙型肝炎病毒
<400>61
gccagccccc ugaugggggc gacacuccac cauagaucac uccccuguga ggaacuacug 60
ucuucacgca gaaagcgucu agccauggcg uuaguaugag ugucgugcag ccuccaggac 120
ccccccuccc gggagagcca uaguggucug cggaaccggu gaguacaccg gaauugccag 180
gacgaccggg uccuuucuug gaucaacccg cucaaugccu ggagauuugg gcgugccccc 240
gcgagacugc uagccgagua guguuggguc gcgaaaggcc uugugguacu gccugauagg 300
gugcuugcga gugccccggg aggucucgua gaccgugcau caugagcaca aauccuaaac 360
cucaaagaaa aaccaaacgu aacaccaacc gccgcccaca ggacgucaag uucccgggcg 420
guggucagau cguuggugga guuuaccugu ugccgcgcag gggccccagg uugggugugc 480
gcgcgacuag gaagacuucc gagcggucgc aaccucguga aaggcggcaa ccuaucccca 540
aggcucgccg ccccgagggc agggccuggg cucagcccgg guacccuugg ccccucuaug 600
gcaaugaggg ucuggggugg gcaggguggc uccugucacc ccgcggcucc cggccuaauu 660
ggggccccac ggacccccgg cguaggucgc guaauuuggg uaaggucauc gauacccuca 720
caugcggcuu cgccgaccuc augggguaca uuccgcucgu cggcgccccc cuaggaggcg 780
uugccagggc ccuggcgcau ggcguccggg uucuggagga cggcgugaac uaugcaacag 840
ggaauuugcc cgguugcucu uucucuaucu uccucuuggc uuugcugucc uguuugacug 900
ucccagcuuc cgcuuaugaa gugcgcaacg uguccgggac auaccauguc acgaacgacu 960
gcgccaacuc aagcauugug uaugaggcag cggacauaau caugcacacc ccugggugcg 1020
ugcccugcgu ccgggagggc aauuccuccc gcugcugggu agcgcucacu cccacgcucg 1080
cggccaggaa caggagcauc cccacuacga cgauacgacg ccacgucgau uugcucguug 1140
gggcggcugc cuucugcucc gccauguacg ugggggaucu cugcgggucu guuuuccuag 1200
ucucccaacu guucaccuuc ucaccucgcc gguaugagac gguacaagaa ugcaauugcu 1260
caaucuaucc cggccacgua ucaggucacc gcauggcuug ggauaugaug augaauuggu 1320
cgcccacagc agcucuagug gugucacagu uacuccgaau cccacaagcc gucguggaua 1380
ugguggcagg ggcccacugg gggguucugg cgggucuugc cuacuauucc auggugggga 1440
acugggcuaa agucuugauu gugaugcuac ucuuugccgg cguugacggg accaccaccg 1500
ugacaggggg agcggcggcc uuuggcacca ggagccuugc guccuucuuu acauuagggc 1560
cgucucagaa aauccaacuu guaaacacca acggcaguug gcacaucaau aggacugccu 1620
ugaauuguaa ugacucccuc cagacugggu uccuugcugc gcuguucuau gcacacaaga 1680
ucaacacguc uggaugccca gagcgcaugg ccagcugccg cccuauugac aaguucgcuc 1740
aggggugggg ucccaucacc cauggugcgc cugacaccuc ggaccagagg cccuacugcu 1800
ggcacuacgc accucgaccg ugugguaucg uacccgcguc ggaggugugu ggcccagugu 1860
auuguuucac cccaagcccu guaguggugg ggacgaccga ucgcuucggc guccccacgu 1920
auagcugggg ggagaauaag acggacgugc ugcuccucaa caacacgcgg ccgccgcagg 1980
gcaauugguu cggcugcaca uggaugaaug gcaccggguu caccaagacg ugugggggcc 2040
ccccguguga uaucgggggg gucggcaaca acaccuugac cugccccacg gauugcuucc 2100
ggaagcaccc cgaggccacu uauaccaaau gcggcucggg gccuugguug acgccuaggu 2160
gucuaguuga cuacccauac aggcuuuggc acuaccccug cacugucaac uuuaccaucu 2220
ucaaggucag gauguaugug gggggcgugg agcacaggcu caacgcugcg ugcaacugga 2280
cucgaggaga gcgcugugac cuagaggaca gggacagauc agagcuuagc ccgcugcuac 2340
ugucuacaac agaguggcag auacugcccu guuccuucac cacccuaccg gcucugucca 2400
cuggcuugau ccaccuccau cagaacaucg uggacgugca auaccuguac gguguagggu 2460
cagcaguugu cuccguugug aucagauggg aguacguccu gcugcucuuc cuccuccugg 2520
cggacgcgcg cguuugugcc ugcuuaugga ugaugcuguu gauagcccag gcugaagccg 2580
ccuuggagaa ccugguaguc cucaacgcgg cguccguggc cggagcgcau ggcauccucu 2640
cuuuccuugu guucuucugc gcugccuggu acaucaaagg caagcuagug ccuggggugg 2700
cguaugcucu cuauggugua uggccgcugc uccugcuccu gcuggcguug ccacaacggg 2760
cguacgccau ggaccgggag auggcugcau cgugcggagg cgcgguuuuc gugggucugg 2820
uacucuugac cuugucacca cacuauaaag cauuccuugc caaguccaua uggugguuac 2880
aauauuuaau caccagggcc gaggcgcauu ugcaagugug gguccccccc cucaacguuc 2940
gggggggccg cgaugccauc auccuccuca cgugcgcggu ccacccagag cuaauuuuug 3000
acaucaccaa aauuuugcuc gccauauuug gcccgcucau ggugcuccag gcuggucuaa 3060
cuagagugcc guacuuugug cgcgcucaag ggcucauccg ugugugcaug uuggugcgga 3120
aagucgcugg gggucauuau auccaaaugg cucucaugag guuggccgca cugacgggca 3180
cguacguuua ugaucaucuu acuccgcugc gggacugggc ccaugcgggc uugcgagacc 3240
uugcgguggc aguugagccc gucguuuucu ccaacacaga gaccaagauu aucaccuggg 3300
gggcggacac cgcggcgugu ggggacauca ucuugggucu accugucucc gcccgaaggg 3360
ggagagaggu acuccuagga ccggccgaua acuuuggaga gcaagggugg cgacuccuug 3420
cgcccaucac ggccuacucc caacagacgc ggggcuuacu uggcuguauc aucaccggcc 3480
ucacaggucg agacaagaac caggucgaag gggagguuca ggugguuucc accgcaacac 3540
agucuuucuu ggcaaccugc gucaacggug uguguuggac ugucuaccau ggugccggcu 3600
caaagacccu agccggcccg aaggggccaa ucacccagau guacaccaac guagaccaag 3660
accucguugg cuggcaggcg ccccccgggg cgcguuccau gacgccgugc accugcggca 3720
gcucggaccu uuacuugguc acgaggcaug cugaugucau uccggugcgc cggcggggug 3780
acagcagagg gagccuacuu ucccccaggc ccgucuccua cuugaagggc ucuucaggug 3840
guccacugcu cugccccuug gggcacgucg ugggcaucuu ucgggcugcc gugugcaccc 3900
gggggguugc gaaggcggug gacuucauac ccaucgaguc uauggaaacu accaugcggu 3960
cuccggucuu uacggauaau ucaucucccc cggccguacc gcagacuuuu caaguggccc 4020
aucugcacgc ccccacuggc agcggcaaga gcaccaaggu gccagcugcg uaugcagccc 4080
agggguacaa ggugcuuguc uugaauccau ccguugccgc caccuugggu uuuggggcgu 4140
auauguccaa ggcauacggu gucgacccua acauuagaac ugggguaagg accaucacca 4200
caggcgcucc caucacguac uccaccuacg gcaaguuccu ugccgacggu gguugcuccg 4260
ggggcgcuua cgacaucaua auaugcgaug agugccacuc aaccgacucg acuuccauuu 4320
ugggcauugg cacgguccug gaucaagcgg agacggcugg agcgcgacuc gucgugcucg 4380
ccaccgcuac gccuccggga ucggucacug ugccacaccc caacaucgag gagguggccu 4440
uguccaacac cggagagauu cccuucuaug gcaaagccau cccccucgag gucaucaagg 4500
gggggaggca ucucauuuuc ugucauucua agaagaagug ugaugagcuc gcugcaaagc 4560
ugucgggccu uggggucaac gcuguagcgu acuaccgggg ucuugaugug uccgucauac 4620
caacaagcgg ggacgucguu gucguggcaa cagacgcucu aaugacgggc uacaccggug 4680
acuuugacuc ugugaucgac uguaauacau gugucaccca gacagucgac uucagccugg 4740
accccaccuu caccauugag acgacgaccg ugccccaaga cgcagugucg cgcucgcagc 4800
ggcgagggag gacugguagg gguagagggg gcauauacag guuugugacu ccaggagagc 4860
ggcccucggg cauguucgau uccucggucc ugugugaaug cuaugacgcg ggcugugcuu 4920
gguacgagcu cacgcccgcc gagaccucgg uuaggcugcg ggcuuaccua aauacaccag 4980
gguugcccgu cugccaggac cauuuggagu ucugggaagg cgucuucaca ggccucacuc 5040
auauagaugc ccacuucuug ucucagacua agcaggcagg agacaacuuc cccuaccugg 5100
uggcauacca ggccacagug ugcgccaggg cccaggcacc accuccauca ugggaucaaa 5160
uguggaagug ucucauacgg cuaaaaccua cacuacacgg gccaacaccc cuguuguaca 5220
ggcuaggagc cguccaaaac gaggucaccc ucacacaccc caugaccaaa uacaucauga 5280
caugcauguc ggcugaccua gaggucguca ccagcacuug ggugcuggug ggcggggucc 5340
ucgcagcuuu ggccgcguac ugcuugacaa cgggcagcgu gguuaucaua ggcaggauca 5400
ucuuguccgg aaggccggcu aucauucccg auagggaagu ucucuaccag gaguucgaug 5460
aaauggaaga gugcgccuca caccuucccu acaucgaaca aggaaugcag cucgccgagc 5520
aauucaagca gaaggcgcuc ggguuguugc aaacggccac caagcaagcg gaggccgcug 5580
cucccguggu ggaguccaaa uggcaagccc uugaggccuu cugggcgaag cacaugugga 5640
acuucaucag cgggauacag uaucuagcag gcuuguccac ucugccugga aaccccgcga 5700
uagcaucgcu gauggcauuu acagccucua ucacuagccc gcucaccacc cuacauaccc 5760
uucuauuuaa caucuugggg ggaugggugg ccgcccaacu cgcccccccc agcgcugcuu 5820
cagccuucgu aggcgccggc aucgccggcg cggcuguugg cagcauaggu cuugggaagg 5880
ugcucgugga cauccuagcg gguuauggag cagggguggc aggcgcacuc guggccuuca 5940
aggucaugag cggcgaagug cccuccacug aggaccuggu caacuuacuc ccugccaucc 6000
ucuccccugg ugcccugguc gucggggucg ugugcgcagc gauacugcgu cggcaugugg 6060
gcccagggga gggggccgug caguggauga accggcugau agcguucgcu ucgcggggua 6120
accacgucuc ccccacgcac uaugugccug agagcgacgc cgcagcgcgu gucacccaga 6180
uccucuccag ccuuaccauc acucagcugc uaaagaggcu ccaccagugg auuaauaagg 6240
acuguuccac gccaugcucc gguucguggc ucagggaugu uugggacugg auaugcacgg 6300
uuuugaccga cuucaaaacc uggcuccagu ccaagcuccu gccacgguug ccgggacucc 6360
cuuucuuuuc augucaacgu ggauauaaag gagucuggcu gggagauggc guuaugcaaa 6420
cuaccugucc auguggugca caaaucagcg gacaugucaa aaacggcucc augaagaucg 6480
uggggccuaa aaccugcagc aacacguggc acgggacguu ccccaucaac gcauacacca 6540
caggccccug cacacccucc ccggcgccga acuauuccaa ggcguugugg cgaguggcug 6600
cugaggagua uguggagguc acgcgggugg gggauuucca cuacgugacg ggcaugacca 6660
cugacaacgu aaaaugccca ugccaggucc cggcccccga auucuucacg gaguuggaug 6720
gggugcggcu gcacagguac gcuccggcgu gcaagccucu cuuacgggau gaggucacau 6780
uccaggucgg gcucaaccag uauccgguug gaucacagcu uccaugugag cccgagccgg 6840
auguaacagu gcucacuucc augcucaccg accccuccca uauuacagca gagacggcua 6900
agcguaggcu ggccagaggg uccccccccu cuuuggccag cuccucagcu agccaguugu 6960
cugcgccuuc cuugaaggcg acaugcacua cccaccauga cuccccagau gcugaccuca 7020
ucgaggccaa ccuccugugg cggcaggaga ugggcgggaa caucacccgc guggagucag 7080
agaacaaggu aguaauucug gacucuuuug aaccgcuucg agcggaggag gaugauaggg 7140
aaguguccgu agcggcggag auccugcgga gaaccaggaa auuccccgca gcgaugccca 7200
uaugggcacg gccggacuac aacccaccac uccuagaguc uuggaagaac ccagacuacg 7260
ucccuccagu gguacacggg ugcccauuac caccuauuaa ggccccuccg auaccaccuc 7320
cacggagaaa gaggacgguc auccugacag aauccaccgu gucuucugcc uuggcggagc 7380
uugcuacaaa gaccuuuggc agcuccggau cgucggccgu ugacagcggc acagcgacug 7440
gcccuccuga ucaguccucc ggugacggag auacaggauc cgacgcugag ucgugcuccu 7500
ccaugccccc ccuugagggg gagccggggg accccgaucu cagcgacggg ucuuggucua 7560
ccgugagcga ggaggccggu gaggacgucg ucugcugcuc gauguccuac acauggacag 7620
gcgccuuaau cacaccgugc gccgcagagg agagcaagcu gccuaucaac gcguugagca 7680
acucuuugcu gcgccaccac aacauggucu augccacaac aucccgcagc gcgggccaac 7740
ggcagaagaa ggucacuuuu gacagagugc agguccugga cgaccauuac cgggacgugc 7800
ucaaggagau gaaggcgaag gcguccacag uuaaggcuaa acuucuaccu guagaagaag 7860
ccugcaggcu gacgccccca cacucggcca gauccaaguu uggcuauggg gcgaaggacg 7920
uccggaaccu auccagcaag gccgucaacc acauccacuc cguguggaag gacuugcugg 7980
aagacucuga gacgccgauu gacaccacca ucauggcaaa aaaugagguc uuuuguguuc 8040
aaccagagaa aggaggccgc aagucagcuc gucuuaucgu auucccagac uuggggguuc 8100
gugugugcga gaaaauggcc cuuuacgacg ugguuuccac ucuuccucag gccgugaugg 8160
gcuccucaua cggguuccag uacucuccug gacagcgggu cgaguuccug gugaaugccu 8220
ggaaaucaaa gaagaacccu augggcuucg cauaugacac ccgcuguuuu gacucaacgg 8280
ucacugagag ugacauccgu guugaggagu caauuuacca auguugugac uuggcccccg 8340
aggccagaca ggucauaagg ucgcucacgg agcggcuuua uaucgggggc ccccugacua 8400
auucaaaagg gcagagcugc ggcuaucgcc ggugccgcgc cagcggugug cugacgacca 8460
gcugcgguaa uacccucaca uguuacuuga aggcuucugc agccugucga gcugcaaagc 8520
uccaggacug cacaauguua gugugcggag acgaccuugu cguuaucugu gaaagugcgg 8580
gaacccagga ggacgcggcg agccuacgag ucuucacgga ggcuaugacu agguacucug 8640
ccccccccgg ggacccgccc cagccagaau acgacuugga gcugauaaca ucaugcuccu 8700
ccaacgucuc ggucgcgcac gaugcacuug gcaagcgggu guauuaucug acccgcgacc 8760
ccaccacccc ccuugcgcgg gcugcguggg agacagcaag acacacucca guuaacuccu 8820
ggcuaggcaa caucaucaug uaugcgccca cccuaugggc aaggaugauu cugaugaccc 8880
acuucuuuuc cauccuucua gcucaggaac aacuugaaaa agcccuagau ugucagaucu 8940
acggggccac uuacuccauu gagccacuug accuaccuca gaucauucag cgacuccacg 9000
gccuuagcgc auuuucacuc cauagcuacu cuccagguga gaucaauagg guggcuucau 9060
gccucaggaa acuuggggua ccacccuugc gagucuggag acaucgggcc agaagugucc 9120
gcgcuaagcu acugucccag ggggggaggg ccgccacuug uggcaaauac cucuucaacu 9180
gggcaguaag gaccaagcuc aaacucacuc caauuccggc ugcgucccag uuggacuugu 9240
ccggcugguu cauugcuggu uacagcgggg gagacauaua ucacagccug ucucgcgccc 9300
gaccccgcug guucaugugg ugccuacucc uacuuuccgu agggguaggc aucuaucugc 9360
uccccaaucg augaacgggg ggcuaaacac uccaggccaa uaggccauuc uguuuuuuuu 9420
uuuuuuuuuu uuuuuuuuuu uuuuuuuuuu uuuuuuuuuu uuuuuuccuu uuuuuuuuuu 9480
uuuuucccuu ucuuuuggug gcuccaucuu agcccuaguc acggcuagcu gugaaagguc 9540
cgugagccgc augacugcag agagugcuga uacuggccuc ucugcagauc augu 9594
<210>62
<211>3010
<212>PRT
<213>丙型肝炎病毒
<400>62
Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Thr Lys Arg Asn Thr Asn
1 5 10 15
Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gly Gly Gln Ile Val Gly
20 25 30
Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Arg Leu Gly Val Arg Ala
35 40 45
Thr Arg Lys Thr Ser Glu Arg Ser Gln Pro Arg Glu Arg Arg Gln Pro
50 55 60
Ile Pro Lys Ala Arg Arg Pro Glu Gly Arg Ala Trp Ala Gln Pro Gly
65 70 75 80
Tyr Pro Trp Pro Leu Tyr Gly Asn Glu Gly Leu Gly Trp Ala Gly Trp
85 90 95
Leu Leu Ser Pro Arg Gly Ser Arg Pro Asn Trp Gly Pro Thr Asp Pro
100 105 110
Arg Arg Arg Ser Arg Asn Leu Gly Lys Val Ile Asp Thr Leu Thr Cys
115 120 125
Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Leu Val Gly Ala Pro Leu
130 135 140
Gly Gly Val Ala Arg Ala Leu Ala His Gly Val Arg Val Leu Glu Asp
145 150 155 160
Gly Val Asn Tyr Ala Thr Gly Asn Leu Pro Gly Cys Ser Phe Ser Ile
165 170 175
Phe Leu Leu Ala Leu Leu Ser Cys Leu Thr Val Pro Ala Ser Ala Tyr
180 185 190
Glu Val Arg Asn Val Ser Gly Thr Tyr His Val Thr Asn Asp Cys Ala
195 200 205
Asn Ser Ser Ile Val Tyr Glu Ala Ala Asp Ile Ile Met His Thr Pro
210 215 220
Gly Cys Val Pro Cys Val Arg Glu Gly Asn Ser Ser Arg Cys Trp Val
225 230 235 240
Ala Leu Thr Pro Thr Leu Ala Ala Arg Asn Arg Ser Ile Pro Thr Thr
245 250 255
Thr Ile Arg Arg His Val Asp Leu Leu Val Gly Ala Ala Ala Phe Cys
260 265 270
Ser Ala Met Tyr Val Gly Asp Leu Cys Gly Ser Val Phe Leu Val Ser
275 280 285
Gln Leu Phe Thr Phe Ser Pro Arg Arg Tyr Glu Thr Val Gln Glu Cys
290 295 300
Asn Cys Ser Ile Tyr Pro Gly His Val Ser Gly His Arg Met Ala Trp
305 3l0 315 320
Asp Met Met Met Asn Trp Ser Pro Thr Ala Ala Leu Val Val Ser Gln
325 330 335
Leu Leu Arg Ile Pro Gln Ala Val Val Asp Met Val Ala Gly Ala His
340 345 350
Trp Gly Val Leu Ala Gly Leu Ala Tyr Tyr Ser Met Val Gly Asn Trp
355 360 365
Ala Lys Val Leu Ile Val Met Leu Leu Phe Ala Gly Val Asp Gly Thr
370 375 380
Thr Thr Val Thr Gly Gly Ala Ala Ala Phe Gly Thr Arg Ser Leu Ala
385 390 395 400
Ser Phe Phe Thr Leu Gly Pro Ser Gln Lys Ile Gln Leu Val Asn Thr
405 410 415
Asn Gly Ser Trp His Ile Asn Arg Thr Ala Leu Asn Cys Asn Asp Ser
420 425 430
Leu Gln Thr Gly Phe Leu Ala Ala Leu Phe Tyr Ala His Lys Ile Asn
435 440 445
Thr Ser Gly Cys Pro Glu Arg Met Ala Ser Cys Arg Pro Ile Asp Lys
450 455 460
Phe Ala Gln Gly Trp Gly Pro Ile Thr His Gly Ala Pro Asp Thr Ser
465 470 475 480
Asp Gln Arg Pro Tyr Cys Trp His Tyr Ala Pro Arg Pro Cys Gly Ile
485 490 495
Val Pro Ala Ser Glu Val Cys Gly Pro Val Tyr Cys Phe Thr Pro Ser
500 505 510
Pro Val Val Val Gly Thr Thr Asp Arg Phe Gly Val Pro Thr Tyr Ser
515 520 525
Trp Gly Glu Asn Lys Thr Asp Val Leu Leu Leu Asn Asn Thr Arg Pro
530 535 540
Pro Gln Gly Asn Trp Phe Gly Cys Thr Trp Met Asn Gly Thr Gly Phe
545 550 555 560
Thr Lys Thr Cys Gly Gly Pro Pro Cys AspIle Gly Gly Val Gly Asn
565 570 575
Asn Thr Leu Thr Cys Pro Thr Asp Cys Phe Arg Lys His Pro Glu Ala
580 585 590
Thr Tyr Thr Lys Cys Gly Ser Gly Pro Trp Leu Thr Pro Arg Cys Leu
595 600 605
Val Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe
610 615 620
Thr Ile Phe Lys Val Arg Met Tyr Val Gly Gly Val Glu His Arg Leu
625 630 635 640
Asn Ala Ala Cys Asn Trp Thr Arg Gly Glu Arg Cys Asp Leu Glu Asp
645 650 655
Arg Asp Arg Ser Glu Leu Ser Pro Leu Leu Leu Ser Thr Thr Glu Trp
660 665 670
Gln Ile Leu Pro Cys Ser Phe Thr Thr Leu Pro Ala Leu Ser Thr Gly
675 680 685
Leu Ile His Leu His Gln Asn Ile Val Asp Val Gln Tyr Leu Tyr Gly
690 695 700
Val Gly Ser Ala Val Val Ser Val Val Ile Arg Trp Glu Tyr Val Leu
705 710 715 720
Leu Leu Phe Leu Leu Leu Ala Asp Ala Arg Val Cys Ala Cys Leu Trp
725 730 735
Met Met Leu Leu Ile Ala Gln Ala Glu Ala Ala Leu Glu Asn Leu Val
740 745 750
Val Leu Asn Ala Ala Ser Val Ala Gly Ala His Gly Ile Leu Ser Phe
755 760 765
Leu Val Phe Phe Cys Ala Ala Trp Tyr Ile Lys Gly Lys Leu Val Pro
770 775 780
Gly Val Ala Tyr Ala Leu Tyr Gly Val Trp Pro Leu Leu Leu Leu Leu
785 790 795 800
Leu Ala Leu Pro Gln Arg Ala Tyr Ala Met Asp Arg Glu Met Ala Ala
805 810 815
Ser Cys Gly Gly Ala Val Phe Val Gly Leu Val Leu Leu Thr Leu Ser
820 825 830
Pro His Tyr Lys Ala Phe Leu Ala Lys Ser Ile Trp Trp Leu Gln Tyr
835 840 845
Leu Ile Thr Arg Ala Glu Ala His Leu Gln Val Trp Val Pro Pro Leu
850 855 860
Asn Val Arg Gly Gly Arg Asp Ala Ile Ile Leu Leu Thr Cys Ala Val
865 870 875 880
His Pro Glu Leu Ile Phe Asp Ile Thr Lys Ile Leu Leu Ala Ile Phe
885 890 895
Gly Pro Leu Met Val Leu Gln Ala Gly Leu Thr Arg Val Pro Tyr Phe
900 905 910
Val Arg Ala Gln Gly Leu Ile Arg Val Cys Met Leu Val Arg Lys Val
915 920 925
Ala Gly Gly His Tyr Ile Gln Met Ala Leu Met Arg Leu Ala Ala Leu
930 935 940
Thr Gly Thr Tyr Val Tyr Asp His Leu Thr Pro Leu Arg Asp Trp Ala
945 950 955 960
His Ala Gly Leu Arg Asp Leu Ala Val Ala Val Glu Pro Val Val Phe
965 970 975
Ser Asn Thr Glu Thr Lys Ile Ile Thr Trp Gly Ala Asp Thr Ala Ala
980 985 990
Cys Gly Asp Ile Ile Leu Gly Leu Pro Val Ser Ala Arg Arg Gly Arg
995 1000 1005
Glu Val Leu Leu Gly Pro Ala Asp Asn Phe Gly Glu Gln Gly Trp
1010 1015 1020
Arg Leu Leu Ala Pro Ile Thr Ala Tyr Ser Gln Gln Thr Arg Gly
1025 1030 1035
Leu Leu Gly Cys Ile Ile Thr Gly Leu Thr Gly Arg Asp Lys Asn
1040 1045 1050
Gln Val Glu Gly Glu Val Gln Val Val Ser Thr Ala Thr Gln Ser
1055 1060 1065
Phe Leu Ala Thr Cys Val Asn Gly Val Cys Trp Thr Val Tyr His
1070 1075 1080
Gly Ala Gly Ser Lys Thr Leu Ala Gly Pro Lys Gly Pro Ile Thr
1085 1090 1095
Gln Met Tyr Thr Asn Val Asp Gln Asp Leu Val Gly Trp Gln Ala
1100 1105 1110
Pro Pro Gly Ala Arg Ser Met Thr Pro Cys Thr Cys Gly Ser Ser
1115 1120 1125
Asp Leu Tyr Leu Val Thr Arg His Ala Asp Val Ile Pro Val Arg
1130 1135 1140
Arg Arg Gly Asp Ser Arg Gly Ser Leu Leu Ser Pro Arg Pro Val
1145 1150 1155
Ser Tyr Leu Lys Gly Ser Ser Gly Gly Pro Leu Leu Cys Pro Leu
1160 1165 1170
Gly His Val Val Gly Ile Phe Arg Ala Ala Val Cys Thr Arg Gly
1175 1180 1185
Val Ala Lys Ala Val Asp Phe Ile Pro Ile Glu Ser Met Glu Thr
1190 1195 1200
Thr Met Arg Ser Pro Val Phe Thr Asp Asn Ser Ser Pro Pro Ala
1205 1210 1215
Val Pro Gln Thr Phe Gln Val Ala His Leu His Ala Pro Thr Gly
1220 1225 1230
Ser Gly Lys Ser Thr Lys Val Pro Ala Ala Tyr Ala Ala Gln Gly
1235 1240 1245
Tyr Lys Val Leu Val Leu Asn Pro Ser Val Ala Ala Thr Leu Gly
1250 1255 1260
Phe Gly Ala Tyr Met Ser Lys Ala Tyr Gly Val Asp Pro Asn Ile
1265 1270 1275
Arg Thr Gly Val Arg Thr Ile Thr Thr Gly Ala Pro Ile Thr Tyr
1280 1285 1290
Ser Thr Tyr Gly Lys Phe Leu Ala Asp Gly Gly Cys Ser Gly Gly
1295 1300 1305
Ala Tyr Asp Ile Ile Ile Cys Asp Glu Cys His Ser Thr Asp Ser
1310 1315 1320
Thr Ser Ile Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr
1325 1330 1335
Ala Gly Ala Arg Leu Val Val Leu Ala Thr Ala Thr Pro Pro Gly
1340 1345 1350
Ser Val Thr Val Pro His Pro Asn Ile Glu Glu Val Ala Leu Ser
1355 1360 1365
Asn Thr Gly Glu Ile Pro Phe Tyr Gly Lys Ala Ile Pro Leu Glu
1370 1375 1380
Val Ile Lys Gly Gly Arg His Leu Ile Phe Cys His Ser Lys Lys
1385 1390 1395
Lys Cys Asp Glu Leu Ala Ala Lys Leu Ser Gly Leu Gly Val Asn
1400 1405 1410
Ala Val Ala Tyr Tyr Arg Gly Leu Asp Val Ser Val Ile Pro Thr
1415 1420 1425
Ser Gly Asp Val Val Val Val Ala Thr Asp Ala Leu Met Thr Gly
1430 1435 1440
Tyr Thr Gly Asp Phe Asp Ser Val Ile Asp Cys Asn Thr Cys Val
1445 1450 1455
Thr Gln Thr Val Asp Phe Ser Leu Asp Pro Thr Phe Thr Ile Glu
1460 1465 1470
Thr Thr Thr Val Pro Gln Asp Ala Val Ser Arg Ser Gln Arg Arg
1475 1480 1485
Gly Arg Thr Gly Arg Gly Arg Gly Gly Ile Tyr Arg Phe Val Thr
1490 1495 1500
Pro Gly Glu Arg Pro Ser Gly Met Phe Asp Ser Ser Val Leu Cys
1505 1510 1515
Glu Cys Tyr Asp Ala Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala
1520 1525 1530
Glu Thr Ser Val Arg Leu Arg Ala Tyr Leu Asn Thr Pro Gly Leu
1535 1540 1545
Pro Val Cys Gln Asp His Leu Glu Phe Trp Glu Gly Val Phe Thr
1550 1555 1560
Gly Leu Thr His Ile Asp Ala His Phe Leu Ser Gln Thr Lys Gln
1565 1570 1575
Ala Gly Asp Asn Phe Pro Tyr Leu Val Ala Tyr Gln Ala Thr Val
1580 1585 1590
Cys Ala Arg Ala Gln Ala Pro Pro Pro Ser Trp Asp Gln Met Trp
1595 1600 1605
Lys Cys Leu Ile Arg Leu Lys Pro Thr Leu His Gly Pro Thr Pro
1610 1615 1620
Leu Leu Tyr Arg Leu Gly Ala Val Gln Asn Glu Val Thr Leu Thr
1625 1630 1635
His Pro Met Thr Lys Tyr Ile Met Thr Cys Met Ser Ala Asp Leu
1640 1645 1650
Glu Val Val Thr Ser Thr Trp Val Leu Val Gly Gly Val Leu Ala
1655 1660 1665
Ala Leu Ala Ala Tyr Cys Leu Thr Thr Gly Ser Val Val Ile Ile
1670 1675 1680
Gly Arg Ile Ile Leu Ser Gly Arg Pro Ala Ile Ile Pro Asp Arg
1685 1690 1695
Glu Val Leu Tyr Gln Glu Phe Asp Glu Met Glu Glu Cys Ala Ser
1700 1705 1710
His Leu Pro Tyr Ile Glu Gln Gly Met Gln Leu Ala Glu Gln Phe
1715 1720 1725
Lys Gln Lys Ala Leu Gly Leu Leu Gln Thr Ala Thr Lys Gln Ala
1730 1735 1740
Glu Ala Ala Ala Pro Val Val Glu Ser Lys Trp Gln Ala Leu Glu
1745 1750 1755
Ala Phe Trp Ala Lys His Met Trp Asn Phe Ile Ser Gly Ile Gln
1760 1765 1770
Tyr Leu Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Ile Ala
1775 1780 1785
Ser Leu Met Ala Phe Thr Ala Ser Ile Thr Ser Pro Leu Thr Thr
1790 1795 1800
Leu His Thr Leu Leu Phe Asn Ile Leu Gly Gly Trp Val Ala Ala
1805 1810 1815
Gln Leu Ala Pro Pro Ser Ala Ala Ser Ala Phe Val Gly Ala Gly
1820 1825 1830
Ile Ala Gly Ala Ala Val Gly Ser Ile Gly Leu Gly Lys Val Leu
1835 1840 1845
Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu
1850 1855 1860
Val Ala Phe Lys Val Met Ser Gly Glu Val Pro Ser Thr Glu Asp
1865 1870 1875
Leu Val Asn Leu Leu Pro Ala Ile Leu Ser Pro Gly Ala Leu Val
1880 1885 1890
Val Gly Val Val Cys Ala Ala Ile Leu Arg Arg His Val Gly Pro
1895 1900 1905
Gly Glu Gly Ala Val Gln Trp Met Asn Arg Leu Ile Ala Phe Ala
1910 1915 1920
Ser Arg Gly Asn His Val Ser Pro Thr His Tyr Val Pro Glu Ser
1925 1930 1935
Asp Ala Ala Ala Arg Val Thr Gln Ile Leu Ser Ser Leu Thr Ile
1940 1945 1950
Thr Gln Leu Leu Lys Arg Leu His Gln Trp Ile Asn Lys Asp Cys
1955 1960 1965
Ser Thr Pro Cys Ser Gly Ser Trp Leu Arg Asp Val Trp Asp Trp
1970 1975 1980
Ile Cys Thr Val Leu Thr Asp Phe Lys Thr Trp Leu Gln Ser Lys
1985 1990 1995
Leu Leu Pro Arg Leu Pro Gly Leu Pro Phe Phe Ser Cys Gln Arg
2000 2005 2010
Gly Tyr Lys Gly Val Trp Leu Gly Asp Gly Val Met Gln Thr Thr
2015 2020 2025
Cys Pro Cys Gly Ala Gln Ile Ser Gly His Val Lys Asn Gly Ser
2030 2035 2040
Met Lys Ile Val Gly Pro Lys Thr Cys Ser Asn Thr Trp His Gly
2045 2050 2055
Thr Phe Pro Ile Asn Ala Tyr Thr Thr Gly Pro Cys Thr Pro Ser
2060 2065 2070
Pro Ala Pro Asn Tyr Ser Lys Ala Leu Trp Arg Val Ala Ala Glu
2075 2080 2085
Glu Tyr Val Glu Val Thr Arg Val Gly Asp Phe His Tyr Val Thr
2090 2095 2100
Gly Met Thr Thr Asp Asn Val Lys Cys Pro Cys Gln Val Pro Ala
2105 2110 2115
Pro Glu Phe Phe Thr Glu Leu Asp Gly Val Arg Leu His Arg Tyr
2120 2125 2130
Ala Pro Ala Cys Lys Pro Leu Leu Arg Asp Glu Val Thr Phe Gln
2135 2140 2145
Val Gly Leu Asn Gln Tyr Pro Val Gly Ser Gln Leu Pro Cys Glu
2150 2155 2160
Pro Glu Pro Asp Val Thr Val Leu Thr Ser Met Leu Thr Asp Pro
2165 2170 2175
Ser His Ile Thr Ala Glu Thr Ala Lys Arg Arg Leu Ala Arg Gly
2180 2185 2190
Ser Pro Pro Ser Leu Ala Ser Ser Ser Ala Ser Gln Leu Ser Ala
2195 2200 2205
Pro Ser Leu Lys Ala Thr Cys Thr Thr His His Asp Ser Pro Asp
2210 2215 2220
Ala Asp Leu Ile Glu Ala Asn Leu Leu Trp Arg Gln Glu Met Gly
2225 2230 2235
Gly Asn Ile Thr Arg Val Glu Ser Glu Asn Lys Val Val Ile Leu
2240 2245 2250
Asp Ser Phe Glu Pro Leu Arg Ala Glu Glu Asp Asp Arg Glu Val
2255 2260 2265
Ser Val Ala Ala Glu Ile Leu Arg Arg Thr Arg Lys Phe Pro Ala
2270 2275 2280
Ala Met Pro Ile Trp Ala Arg Pro Asp Tyr Asn Pro Pro Leu Leu
2285 2290 2295
Glu Ser Trp Lys Asn Pro Asp Tyr Val Pro Pro Val Val His Gly
2300 2305 2310
Cys Pro Leu Pro Pro Ile Lys Ala Pro Pro Ile Pro Pro Pro Arg
2315 2320 2325
Arg Lys Arg Thr Val Ile Leu Thr Glu Ser Thr Val Ser Ser Ala
2330 2335 2340
Leu Ala Glu Leu Ala Thr Lys Thr Phe Gly Ser Ser Gly Ser Ser
2345 2350 2355
Ala Val Asp Ser Gly Thr Ala Thr Gly Pro Pro Asp Gln Ser Ser
2360 2365 2370
Gly Asp Gly Asp Thr Gly Ser Asp Ala Glu Ser Cys Ser Ser Met
2375 2380 2385
Pro Pro Leu Glu Gly Glu Pro Gly Asp Pro Asp Leu Ser Asp Gly
2390 2395 2400
Ser Trp Ser Thr Val Ser Glu Glu Ala Gly Glu Asp Val Val Cys
2405 2410 2415
Cys Ser Met Ser Tyr Thr Trp Thr Gly Ala Leu Ile Thr Pro Cys
2420 2425 2430
Ala Ala Glu Glu Ser Lys Leu Pro Ile Asn Ala Leu Ser Asn Ser
2435 2440 2445
Leu Leu Arg His His Asn Met Val Tyr Ala Thr Thr Ser Arg Ser
2450 2455 2460
Ala Gly Gln Arg Gln Lys Lys Val Thr Phe Asp Arg Val Gln Val
2465 2470 2475
Leu Asp Asp His Tyr Arg Asp Val Leu Lys Glu Met Lys Ala Lys
2480 2485 2490
Ala Ser Thr Val Lys Ala Lys Leu Leu Pro Val Glu Glu Ala Cys
2495 2500 2505
Arg Leu Thr Pro Pro His Ser Ala Arg Ser Lys Phe Gly Tyr Gly
2510 2515 2520
Ala Lys Asp Val Arg Asn Leu Ser Ser Lys Ala Val Asn His Ile
2525 2530 2535
His Ser Val Trp Lys Asp Leu Leu Glu Asp Ser Glu Thr Pro Ile
2540 2545 2550
Asp Thr Thr Ile Met Ala Lys Asn Glu Val Phe Cys Val Gln Pro
2555 2560 2565
Glu Lys Gly Gly Arg Lys Ser Ala Arg Leu Ile Val Phe Pro Asp
2570 2575 2580
Leu Gly Val Arg Val Cys Glu Lys Met Ala Leu Tyr Asp Val Val
2585 2590 2595
Ser Thr Leu Pro Gln Ala Val Met Gly Ser Ser Tyr Gly Phe Gln
2600 2605 2610
Tyr Ser Pro Gly Gln Arg Val Glu Phe Leu Val Asn Ala Trp Lys
2615 2620 2625
Ser Lys Lys Asn Pro Met Gly Phe Ala Tyr Asp Thr Arg Cys Phe
2630 2635 2640
Asp Ser Thr Val Thr Glu Ser Asp Ile Arg Val Glu Glu Ser Ile
2645 2650 2655
Tyr Gln Cys Cys Asp Leu Ala Pro Glu Ala Arg Gln Val Ile Arg
2660 2665 2670
Ser Leu Thr Glu Arg Leu Tyr Ile Gly Gly Pro Leu Thr Asn Ser
2675 2680 2685
Lys Gly Gln Ser Cys Gly Tyr Arg Arg Cys Arg Ala Ser Gly Val
2690 2695 2700
Leu Thr Thr Ser Cys Gly Asn Thr Leu Thr Cys Tyr Leu Lys Ala
2705 2710 2715
Ser Ala Ala Cys Arg Ala Ala Lys Leu Gln Asp Cys Thr Met Leu
2720 2725 2730
Val Cys Gly Asp Asp Leu Val Val Ile Cys Glu Ser Ala Gly Thr
2735 2740 2745
Gln Glu Asp Ala Ala Ser Leu Arg Val Phe Thr Glu Ala Met Thr
2750 2755 2760
Arg Tyr Ser Ala Pro Pro Gly Asp Pro Pro Gln Pro Glu Tyr Asp
2765 2770 2775
Leu Glu Leu Ile Thr Ser Cys Ser Ser Asn Val Ser Val Ala His
2780 2785 2790
Asp Ala Leu Gly Lys Arg Val Tyr Tyr Leu Thr Arg Asp Pro Thr
2795 2800 2805
Thr Pro Leu Ala Arg Ala Ala Trp Glu Thr Ala Arg His Thr Pro
2810 2815 2820
Val Asn Ser Trp Leu Gly Asn Ile Ile Met Tyr Ala Pro Thr Leu
2825 2830 2835
Trp Ala Arg Met Ile Leu Met Thr His Phe Phe Ser Ile Leu Leu
2840 2845 2850
Ala Gln Glu Gln Leu Glu Lys Ala Leu Asp Cys Gln Ile Tyr Gly
2855 2860 2865
Ala Thr Tyr Ser Ile Glu Pro Leu Asp Leu Pro Gln Ile Ile Gln
2870 2875 2880
Arg Leu His Gly Leu Ser Ala Phe Ser Leu His Ser Tyr Ser Pro
2885 2890 2895
Gly Glu Ile Asn Arg Val Ala Ser Cys Leu Arg Lys Leu Gly Val
2900 2905 2910
Pro Pro Leu Arg Val Trp Arg His Arg Ala Arg Ser Val Arg Ala
2915 2920 2925
Lys Leu Leu Ser Gln Gly Gly Arg Ala Ala Thr Cys Gly Lys Tyr
2930 2935 2940
Leu Phe Asn Trp Ala Val Arg Thr Lys Leu Lys Leu Thr Pro Ile
2945 2950 2955
Pro Ala Ala Ser Gln Leu Asp Leu Ser Gly Trp Phe Ile Ala Gly
2960 2965 2970
Tyr Ser Gly Gly Asp Ile Tyr His Ser Leu Ser Arg Ala Arg Pro
2975 2980 2985
Arg Trp Phe Met Trp Cys Leu Leu Leu Leu Ser Val Gly Val Gly
2990 2995 3000
Ile Tyr Leu Leu Pro Asn Arg
3005 3010
<210>63
<211>9594
<212>RNA
<213>丙型肝炎病毒
<400>63
gccagccccc ugaugggggc gacacuccac cauagaucac uccccuguga ggaacuacug 60
ucuucacgca gaaagcgucu agccauggcg uuaguaugag ugucgugcag ccuccaggac 120
ccccccuccc gggagagcca uaguggucug cggaaccggu gaguacaccg gaauugccag 180
gacgaccggg uccuuucuug gaucaacccg cucaaugccu ggagauuugg gcgugccccc 240
gcgagacugc uagccgagua guguuggguc gcgaaaggcc uugugguacu gccugauagg 300
gugcuugcga gugccccggg aggucucgua gaccgugcau caugagcaca aauccuaaac 360
cucaaagaaa aaccaaacgu aacaccaacc gccgcccaca ggacgucaag uucccgggcg 420
guggucagau cguuggugga guuuaccugu ugccgcgcag gggccccagg uugggugugc 480
gcgcgacuag gaagacuucc gagcggucgc aaccucguga aaggcggcaa ccuaucccca 540
aggcucgccg ccccgagggc agggccuggg cucagcccgg guacccuugg ccccucuaug 600
gcaaugaggg ucuggggugg gcaggguggc uccugucacc ccgcggcucc cggccuaauu 660
ggggccccac ggacccccgg cguaggucgc guaauuuggg uaaggucauc gauacccuca 720
caugcggcuu cgccgaccuc augggguaca uuccgcucgu cggcgccccc cuaggaggcg 780
uugccagggc ccuggcgcau ggcguccggg uucuggagga cggcgugaac uaugcaacag 840
ggaauuugcc cgguugcucu uucucuaucu uccucuuggc uuugcugucc uguuugacug 900
ucccagcuuc cgcuuaugaa gugcgcaacg uguccgggac auaccauguc acgaacgacu 960
gcgccaacuc aagcauugug uaugaggcag cggacauaau caugcacacc ccugggugcg 1020
ugcccugcgu ccgggagggc aauuccuccc gcugcugggu agcgcucacu cccacgcucg 1080
cggccaggaa caggagcauc cccacuacga cgauacgacg ccacgucgau uugcucguug 1140
gggcggcugc cuucugcucc gccauguacg ugggggaucu cugcgggucu guuuuccuag 1200
ucucccaacu guucaccuuc ucaccucgcc gguaugagac gguacaagaa ugcaauugcu 1260
caaucuaucc cggccacgua ucaggucacc gcauggcuug ggauaugaug augaauuggu 1320
cgcccacagc agcucuagug gugucacagu uacuccgaau cccacaagcc gucguggaua 1380
ugguggcagg ggcccacugg gggguucugg cgggucuugc cuacuauucc auggugggga 1440
acugggcuaa agucuugauu gugaugcuac ucuuugccgg cguugacggg accaccaccg 1500
ugacaggggg agcggcggcc uuuggcacca ggagccuugc guccuucuuu acauuagggc 1560
cgucucagaa aauccaacuu guaaacacca acggcaguug gcacaucaau aggacugccu 1620
ugaauuguaa ugacucccuc cagacugggu uccuugcugc gcuguucuau gcacacaaga 1680
ucaacacguc uggaugccca gagcgcaugg ccagcugccg cccuauugac aaguucgcuc 1740
aggggugggg ucccaucacc cauggugcgc cugacaccuc ggaccagagg cccuacugcu 1800
ggcacuacgc accucgaccg ugugguaucg uacccgcguc ggaggugugu ggcccagugu 1860
auuguuucac cccaagcccu guaguggugg ggacgaccga ucgcuucggc guccccacgu 1920
auagcugggg ggagaauaag acggacgugc ugcuccucaa caacacgcgg ccgccgcagg 1980
gcaauugguu cggcugcaca uggaugaaug gcaccggguu caccaagacg ugugggggcc 2040
ccccguguga uaucgggggg gucggcaaca acaccuugac cugccccacg gauugcuucc 2100
ggaagcaccc cgaggccacu uauaccaaau gcggcucggg gccuugguug acgccuaggu 2160
gucuaguuga cuacccauac aggcuuuggc acuaccccug cacugucaac uuuaccaucu 2220
ucaaggucag gauguaugug gggggcgugg agcacaggcu caacgcugcg ugcaacugga 2280
cucgaggaga gcgcugugac cuagaggaca gggacagauc agagcuuagc ccgcugcuac 2340
ugucuacaac agaguggcag auacugcccu guuccuucac cacccuaccg gcucugucca 2400
cuggcuugau ccaccuccau cagaacaucg uggacgugca auaccuguac gguguagggu 2460
cagcaguugu cuccguugug aucagauggg aguacguccu gcugcucuuc cuccuccugg 2520
cggacgcgcg cguuugugcc ugcuuaugga ugaugcuguu gauagcccag gcugaagccg 2580
ccuuggagaa ccugguaguc cucaacgcgg cguccguggc cggagcgcau ggcauccucu 2640
cuuuccuugu guucuucugc gcugccuggu acaucaaagg caagcuagug ccuggggugg 2700
cguaugcucu cuauggugua uggccgcugc uccugcuccu gcuggcguug ccacaacggg 2760
cguacgccau ggaccgggag auggcugcau cgugcggagg cgcgguuuuc gugggucugg 2820
uacucuugac cuugucacca cacuauaaag cauuccuugc caaguccaua uggugguuac 2880
aauauuuaau caccagggcc gaggcgcauu ugcaagugug gguccccccc cucaacguuc 2940
gggggggccg cgaugccauc auccuccuca cgugcgcggu ccacccagag cuaauuuuug 3000
acaucaccaa aauuuugcuc gccauauuug gcccgcucau ggugcuccag gcuggucuaa 3060
cuagagugcc guacuuugug cgcgcucaag ggcucauccg ugugugcaug uuggugcgga 3120
aagucgcugg gggucauuau auccaaaugg cucucaugag guuggccgca cugacgggca 3180
cguacguuua ugaucaucuu acuccgcugc gggacugggc ccaugcgggc uugcgagacc 3240
uugcgguggc aguugagccc gucguuuucu ccaacacaga gaccaagauu aucaccuggg 3300
gggcggacac cgcggcgugu ggggacauca ucuugggucu accugucucc gcccgaaggg 3360
ggagagaggu acuccuagga ccggccgaua acuuuggaga gcaagggugg cgacuccuug 3420
cgcccaucac ggccuacucc caacagacgc ggggcuuacu uggcuguauc aucaccggcc 3480
ucacaggucg agacaagaac caggucgaag gggagguuca ggugguuucc accgcaacac 3540
agucuuucuu ggcaaccugc gucaacggug uguguuggac ugucuaccau ggugccggcu 3600
caaagacccu agccggcccg aaggggccaa ucacccagau guacaccaac guagaccaag 3660
accucguugg cuggcaggcg ccccucgggg cgcguuccau gacgccgugc accugcggca 3720
gcucggaccu uuacuugguc acgaggcaug cugaugucau uccggugcgc cggcggggug 3780
acagcagagg gagccuacuu ucccccaggc ccgucuccua cuugaagggc ucuucaggug 3840
guccacugcu cugccccuug gggcacgucg ugggcaucuu ucgggcugcc gugugcaccc 3900
gggggguugc gaaggcggug gacuucauac ccaucgaguc uauggaaacu accaugcggu 3960
cuccggucuu uacggauaau ucaucucccc cggccguacc gcagacuuuu caaguggccc 4020
aucugcacgc ccccacuggc agcggcaaga gcaccaaggu gccagcugcg uaugcagccc 4080
agggguacaa ggugcuuguc uugaauccau ccguugccgc caccuugggu uuuggggcgu 4140
auauguccaa ggcauacggu gucgacccua acauuagaac ugggguaagg accaucacca 4200
caggcgcucc caucacguac uccaccuacg gcaaguuccu ugccgacggu gguugcuccg 4260
ggggcgcuua cgacaucaua auaugcgaug agugccacuc aaccgacucg acuuccauuu 4320
ugggcauugg cacgguccug gaucaagcgg agacggcugg agcgcgacuc gucgugcucg 4380
ccaccgcuac gccuccggga ucggucacug ugccacaccc caacaucgag gagguggccu 4440
uguccaacac cggagagauu cccuucuaug gcaaagccau cccccucgag gucaucaagg 4500
gggggaggca ucucauuuuc ugucauucua agaagaagug ugaugagcuc gcugcaaagc 4560
ugucgggccu uggggucaac gcuguagcgu acuaccgggg ucuugaugug uccgucauac 4620
caacaagcgg ggacgucguu gucguggcaa cagacgcucu aaugacgggc uacaccggug 4680
acuuugacuc ugugaucgac uguaauacau gugucaccca gacagucgac uucagccugg 4740
accccaccuu caccauugag acgacgaccg ugccccaaga cgcagugucg cgcucgcagc 4800
ggcgagggag gacugguagg gguagagggg gcauauacag guuugugacu ccaggagagc 4860
ggcccucggg cauguucgau uccucggucc ugugugaaug cuaugacgcg ggcugugcuu 4920
gguacgagcu cacgcccgcc gagaccucgg uuaggcugcg ggcuuaccua aauacaccag 4980
gguugcccgu cugccaggac cauuuggagu ucugggaagg cgucuucaca ggccucacuc 5040
auauagaugc ccacuucuug ucucagacua agcaggcagg agacaacuuc cccuaccugg 5100
uggcauacca ggccacagug ugcgccaggg cccaggcacc accuccauca ugggaucaaa 5160
uguggaagug ucucauacgg cuaaaaccua cacuacacgg gccaacaccc cuguuguaca 5220
ggcuaggagc cguccaaaac gaggucaccc ucacacaccc caugaccaaa uacaucauga 5280
caugcauguc ggcugaccua gaggucguca ccagcacuug ggugcuggug ggcggggucc 5340
ucgcagcuuu ggccgcguac ugcuugacaa cgggcagcgu gguuaucaua ggcaggauca 5400
ucuuguccgg aaggccggcu aucauucccg auagggaagu ucucuaccag gaguucgaug 5460
aaauggaaga gugcgccuca caccuucccu acaucgaaca aggaaugcag cucgccgagc 5520
aauucaagca gaaggcgcuc ggguuguugc aaacggccac caagcaagcg gaggccgcug 5580
cucccguggu ggaguccaaa uggcaagccc uugaggccuu cugggcgaag cacaugugga 5640
acuucaucag cgggauacag uaucuagcag gcuuguccac ucugccugga aaccccgcga 5700
uagcaucgcu gauggcauuu acagccucua ucacuagccc gcucaccacc cuacauaccc 5760
uucuauuuaa caucuugggg ggaugggugg ccgcccaacu cgcccccccc agcgcugcuu 5820
cagccuucgu aggcgccggc aucgccggcg cggcuguugg cagcauaggu cuugggaagg 5880
ugcucgugga cauccuagcg gguuauggag cagggguggc aggcgcacuc guggccuuca 5940
aggucaugag cggcgaagug cccuccacug aggaccuggu caacuuacuc ccugccaucc 6000
ucuccccugg ugcccugguc gucggggucg ugugcgcagc gauacugcgu cggcaugugg 6060
gcccagggga gggggccgug caguggauga accggcugau agcguucgcu ucgcggggua 6120
accacgucuc ccccacgcac uaugugccug agagcgacgc cgcagcgcgu gucacccaga 6180
uccucuccag ccuuaccauc acucagcugc uaaagaggcu ccaccagugg auuaauaagg 6240
acuguuccac gccaugcucc gguucguggc ucagggaugu uugggacugg auaugcacgg 6300
uuuugaccga cuucaaaacc uggcuccagu ccaagcuccu gccacgguug ccgggacucc 6360
cuuucuuuuc augucaacgu ggauauaaag gagucuggcu gggagauggc guuaugcaaa 6420
cuaccugucc auguggugca caaaucagcg gacaugucaa aaacggcucc augaagaucg 6480
uggggccuaa aaccugcagc aacacguggc acgggacguu ccccaucaac gcauacacca 6540
caggccccug cacacccucc ccggcgccga acuauuccaa ggcguugugg cgaguggcug 6600
cugaggagua uguggagguc acgcgggugg gggauuucca cuacgugacg ggcaugacca 6660
cugacaacgu aaaaugccca ugccaggucc cggcccccga auucuucacg gaguuggaug 6720
gggugcggcu gcacagguac gcuccggcgu gcaagccucu cuuacgggau gaggucacau 6780
uccaggucgg gcucaaccag uauccgguug gaucacagcu uccaugugag cccgagccgg 6840
auguaacagu gcucacuucc augcucaccg accccuccca uauuacagca gagacggcua 6900
agcguaggcu ggccagaggg uccccccccu cuuuggccag cuccucagcu agccaguugu 6960
cugcgccuuc cuugaaggcg acaugcacua cccaccauga cuccccagau gcugaccuca 7020
ucgaggccaa ccuccugugg cggcaggaga ugggcgggaa caucacccgc guggagucag 7080
agaacaaggu aguaauucug gacucuuuug aaccgcuucg agcggaggag gaugauaggg 7140
aaguguccgu agcggcggag auccugcgga gaaccaggaa auuccccgca gcgaugccca 7200
uaugggcacg gccggacuac aacccaccac uccuagaguc uuggaagaac ccagacuacg 7260
ucccuccagu gguacacggg ugcccauuac caccuauuaa ggccccuccg auaccaccuc 7320
cacggagaaa gaggacgguc auccugacag aauccaccgu gucuucugcc uuggcggagc 7380
uugcuacaaa gaccuuuggc agcuccggau cgucggccgu ugacagcggc acagcgacug 7440
gcccuccuga ucaguccucc ggugacggag auacaggauc cgacgcugag ucgugcuccu 7500
ccaugccccc ccuugagggg gagccggggg accccgaucu cagcgacggg ucuuggucua 7560
ccgugagcga ggaggccggu gaggacgucg ucugcugcuc gauguccuac acauggacag 7620
gcgccuuaau cacaccgugc gccgcagagg agagcaagcu gccuaucaac gcguugagca 7680
acucuuugcu gcgccaccac aacauggucu augccacaac aucccgcagc gcgggccaac 7740
ggcagaagaa ggucacuuuu gacagagugc agguccugga cgaccauuac cgggacgugc 7800
ucaaggagau gaaggcgaag gcguccacag uuaaggcuaa acuucuaccu guagaagaag 7860
ccugcaggcu gacgccccca cacucggcca gauccaaguu uggcuauggg gcgaaggacg 7920
uccggaaccu auccagcaag gccgucaacc acauccacuc cguguggaag gacuugcugg 7980
aagacucuga gacgccgauu gacaccacca ucauggcaaa aaaugagguc uuuuguguuc 8040
aaccagagaa aggaggccgc aagucagcuc gucuuaucgu auucccagac uuggggguuc 8100
gugugugcga gaaaauggcc cuuuacgacg ugguuuccac ucuuccucag gccgugaugg 8160
gcuccucaua cggguuccag uacucuccug gacagcgggu cgaguuccug gugaaugccu 8220
ggaaaucaaa gaagaacccu augggcuucg cauaugacac ccgcuguuuu gacucaacgg 8280
ucacugagag ugacauccgu guugaggagu caauuuacca auguugugac uuggcccccg 8340
aggccagaca ggucauaagg ucgcucacgg agcggcuuua uaucgggggc ccccugacua 8400
auucaaaagg gcagagcugc ggcuaucgcc ggugccgcgc cagcggugug cugacgacca 8460
gcugcgguaa uacccucaca uguuacuuga aggcuucugc agccugucga gcugcaaagc 8520
uccaggacug cacaauguua gugugcggag acgaccuugu cguuaucugu gaaagugcgg 8580
gaacccagga ggacgcggcg agccuacgag ucuucacgga ggcuaugacu agguacucug 8640
ccccccccgg ggacccgccc cagccagaau acgacuugga gcugauaaca ucaugcuccu 8700
ccaacgucuc ggucgcgcac gaugcacuug gcaagcgggu guauuaucug acccgcgacc 8760
ccaccacccc ccuugcgcgg gcugcguggg agacagcaag acacacucca guuaacuccu 8820
ggcuaggcaa caucaucaug uaugcgccca cccuaugggc aaggaugauu cugaugaccc 8880
acuucuuuuc cauccuucua gcucaggaac aacuugaaaa agcccuagau ugucagaucu 8940
acggggccac uuacuccauu gagccacuug accuaccuca gaucauucag cgacuccacg 9000
gccuuagcgc auuuucacuc cauagcuacu cuccagguga gaucaauagg guggcuucau 9060
gccucaggaa acuuggggua ccacccuugc gagucuggag acaucgggcc agaagugucc 9120
gcgcuaagcu acugucccag ggggggaggg ccgccacuug uggcaaauac cucuucaacu 9180
gggcaguaag gaccaagcuc aaacucacuc caauuccggc ugcgucccag uuggacuugu 9240
ccggcugguu cauugcuggu uacagcgggg gagacauaua ucacagccug ucucgcgccc 9300
gaccccgcug guucaugugg ugccuacucc uacuuuccgu agggguaggc aucuaucugc 9360
uccccaaucg augaacgggg ggcuaaacac uccaggccaa uaggccauuc uguuuuuuuu 9420
uuuuuuuuuu uuuuuuuuuu uuuuuuuuuu uuuuuuuuuu uuuuuuccuu uuuuuuuuuu 9480
uuuuucccuu ucuuuuggug gcuccaucuu agcccuaguc acggcuagcu gugaaagguc 9540
cgugagccgc augacugcag agagugcuga uacuggccuc ucugcagauc augu 9594
<210>64
<211>3010
<212>PRT
<213>丙型肝炎病毒
<400>64
Met Ser Thr Asn Pro Lys Pro Gln Arg Lys Thr Lys Arg Asn Thr Asn
1 5 10 15
Arg Arg Pro Gln Asp Val Lys Phe Pro Gly Gly Gly Gln Ile Val Gly
20 25 30
Gly Val Tyr Leu Leu Pro Arg Arg Gly Pro Arg Leu Gly Val Arg Ala
35 40 45
Thr Arg Lys Thr Ser Glu Arg Ser Gln Pro Arg Glu Arg Arg Gln Pro
50 55 60
Ile Pro Lys Ala Arg Arg Pro Glu Gly Arg Ala Trp Ala Gln Pro Gly
65 70 75 80
Tyr Pro Trp Pro Leu Tyr Gly Asn Glu Gly Leu Gly Trp Ala Gly Trp
85 90 95
Leu Leu Ser Pro Arg Gly Ser Arg Pro Asn Trp Gly Pro Thr Asp Pro
100 105 110
Arg Arg Arg Ser Arg Asn Leu Gly Lys Val Ile Asp Thr Leu Thr Cys
115 120 125
Gly Phe Ala Asp Leu Met Gly Tyr Ile Pro Leu Val Gly Ala Pro Leu
130 135 140
Gly Gly Val Ala Arg Ala Leu Ala His Gly Val Arg Val Leu Glu Asp
145 150 155 160
Gly Val Asn Tyr Ala Thr Gly Asn Leu Pro Gly Cys Ser Phe Ser Ile
165 170 175
Phe Leu Leu Ala Leu Leu Ser Cys Leu Thr Val Pro Ala Ser Ala Tyr
180 185 190
Glu Val Arg Asn Val Ser Gly Thr Tyr His Val Thr Asn Asp Cys Ala
195 200 205
Asn Ser Ser Ile Val Tyr Glu Ala Ala Asp Ile Ile Met His Thr Pro
210 215 220
Gly Cys Val Pro Cys Val Arg Glu Gly Asn Ser Ser Arg Cys Trp Val
225 230 235 240
Ala Leu Thr Pro Thr Leu Ala Ala Arg Asn Arg Ser Ile Pro Thr Thr
245 250 255
Thr Ile Arg Arg His Val Asp Leu Leu Val Gly Ala Ala Ala Phe Cys
260 265 270
Ser Ala Met Tyr Val Gly Asp Leu Cys Gly Ser Val Phe Leu Val Ser
275 280 285
Gln Leu Phe Thr Phe Ser Pro Arg Arg Tyr Glu Thr Val Gln Glu Cys
290 295 300
Asn Cys Ser Ile Tyr Pro Gly His Val Ser Gly His Arg Met Ala Trp
305 310 315 320
Asp Met Met Met Asn Trp Ser Pro Thr Ala Ala Leu Val Val Ser Gln
325 330 335
Leu Leu Arg Ile Pro Gln Ala Val Val Asp Met Val Ala Gly Ala His
340 345 350
Trp Gly Val Leu Ala Gly Leu Ala Tyr Tyr Ser Met Val Gly Asn Trp
355 360 365
Ala Lys Val Leu Ile Val Met Leu Leu Phe Ala Gly Val Asp Gly Thr
370 375 380
Thr Thr Val Thr Gly Gly Ala Ala Ala Phe Gly Thr Arg Ser Leu Ala
385 390 395 400
Ser Phe Phe Thr Leu Gly Pro Ser Gln Lys Ile Gln Leu Val Asn Thr
405 410 415
Asn Gly Ser Trp His Ile Asn Arg Thr Ala Leu Asn Cys Asn Asp Ser
420 425 430
Leu Gln Thr Gly Phe Leu Ala Ala Leu Phe Tyr Ala His Lys Ile Asn
435 440 445
Thr Ser Gly Cys Pro Glu Arg Met Ala Ser Cys Arg Pro Ile Asp Lys
450 455 460
Phe Ala Gln Gly Trp Gly Pro Ile Thr His Gly Ala Pro Asp Thr Ser
465 470 475 480
Asp Gln Arg Pro Tyr Cys Trp His Tyr Ala Pro Arg Pro Cys Gly Ile
485 490 495
Val Pro Ala Ser Glu Val Cys Gly Pro Val Tyr Cys Phe Thr Pro Ser
500 505 510
Pro Val Val Val Gly Thr Thr Asp Arg Phe Gly Val Pro Thr Tyr Ser
515 520 525
Trp Gly Glu Asn Lys Thr Asp Val Leu Leu Leu Asn Asn Thr Arg Pro
530 535 540
Pro Gln Gly Asn Trp Phe Gly Cys Thr Trp Met Asn Gly Thr Gly Phe
545 550 555 560
Thr Lys Thr Cys Gly Gly Pro Pro Cys Asp Ile Gly Gly Val Gly Asn
565 570 575
Asn Thr Leu Thr Cys Pro Thr Asp Cys Phe Arg Lys His Pro Glu Ala
580 585 590
Thr Tyr Thr Lys Cys Gly Ser Gly Pro Trp Leu Thr Pro Arg Cys Leu
595 600 605
Val Asp Tyr Pro Tyr Arg Leu Trp His Tyr Pro Cys Thr Val Asn Phe
610 615 620
Thr Ile Phe Lys Val Arg Met Tyr Val Gly Gly Val Glu His Arg Leu
625 630 635 640
Asn Ala Ala Cys Asn Trp Thr Arg Gly Glu Arg Cys Asp Leu Glu Asp
645 650 655
Arg Asp Arg Ser Glu Leu Ser Pro Leu Leu Leu Ser Thr Thr Glu Trp
660 665 670
Gln Ile Leu Pro Cys Ser Phe Thr Thr Leu Pro Ala Leu Ser Thr Gly
675 680 685
Leu Ile His Leu His Gln Asn Ile Val Asp Val Gln Tyr Leu Tyr Gly
690 695 700
Val Gly Ser Ala Val Val Ser Val Val Ile Arg Trp Glu Tyr Val Leu
705 710 715 720
Leu Leu Phe Leu Leu Leu Ala Asp Ala Arg Val Cys Ala Cys Leu Trp
725 730 735
Met Met Leu Leu Ile Ala Gln Ala Glu Ala Ala Leu Glu Asn Leu Val
740 745 750
Val Leu Asn Ala Ala Ser Val Ala Gly Ala His Gly Ile Leu Ser Phe
755 760 765
Leu Val Phe Phe Cys Ala Ala Trp Tyr Ile Lys Gly Lys Leu Val Pro
770 775 780
Gly Val Ala Tyr Ala Leu Tyr Gly Val Trp Pro Leu Leu Leu Leu Leu
785 790 795 800
Leu Ala Leu Pro Gln Arg Ala Tyr Ala Met Asp Arg Glu Met Ala Ala
805 810 815
Ser Cys Gly Gly Ala Val Phe Val Gly Leu Val Leu Leu Thr Leu Ser
820 825 830
Pro His Tyr Lys Ala Phe Leu Ala Lys Ser Ile Trp Trp Leu Gln Tyr
835 840 845
Leu Ile Thr Arg Ala Glu Ala His Leu Gln Val Trp Val Pro Pro Leu
850 855 860
Asn Val Arg Gly Gly Arg Asp Ala Ile Ile Leu Leu Thr Cys Ala Val
865 870 875 880
His Pro Glu Leu Ile Phe Asp Ile Thr Lys Ile Leu Leu Ala Ile Phe
885 890 895
Gly Pro Leu Met Val Leu Gln Ala Gly Leu Thr Arg Val Pro Tyr Phe
900 905 910
Val Arg Ala Gln Gly Leu Ile Arg Val Cys Met Leu Val Arg Lys Val
915 920 925
Ala Gly Gly His Tyr Ile Gln Met Ala Leu Met Arg Leu Ala Ala Leu
930 935 940
Thr Gly Thr Tyr Val Tyr Asp His Leu Thr Pro Leu Arg Asp Trp Ala
945 950 955 960
His Ala Gly Leu Arg Asp Leu Ala Val Ala Val Glu Pro Val Val Phe
965 970 975
Ser Asn Thr Glu Thr Lys Ile Ile Thr Trp Gly Ala Asp Thr Ala Ala
980 985 990
Cys Gly Asp Ile Ile Leu Gly Leu Pro Val Ser Ala Arg Arg Gly Arg
995 1000 1005
Glu Val Leu Leu Gly Pro Ala Asp Asn Phe Gly Glu Gln Gly Trp
1010 1015 1020
Arg Leu Leu Ala Pro Ile Thr Ala Tyr Ser Gln Gln Thr Arg Gly
1025 1030 1035
Leu Leu Gly Cys Ile Ile Thr Gly Leu Thr Gly Arg Asp Lys Asn
1040 1045 1050
Gln Val Glu Gly Glu Val Gln Val Val Ser Thr Ala Thr Gln Ser
1055 1060 1065
Phe Leu Ala Thr Cys Val Asn Gly Val Cys Trp Thr Val Tyr His
1070 1075 1080
Gly Ala Gly Ser Lys Thr Leu Ala Gly Pro Lys Gly Pro Ile Thr
1085 1090 1095
Gln Met Tyr Thr Asn Val Asp Gln Asp Leu Val Gly Trp Gln Ala
1100 1105 1110
Pro Leu Gly Ala Arg Ser Met Thr Pro Cys Thr Cys Gly Ser Ser
1115 1120 1125
Asp Leu Tyr Leu Val Thr Arg His Ala Asp Val Ile Pro Val Arg
1130 1135 1140
Arg Arg Gly Asp Ser Arg Gly Ser Leu Leu Ser Pro Arg Pro Val
1145 1150 1155
Ser Tyr Leu Lys Gly Ser Ser Gly Gly Pro Leu Leu Cys Pro Leu
1160 1165 1170
Gly His Val Val Gly Ile Phe Arg Ala Ala Val Cys Thr Arg Gly
1175 1180 1185
Val Ala Lys Ala Val Asp Phe Ile Pro Ile Glu Ser Met Glu Thr
1190 1195 1200
Thr Met Arg Ser Pro Val Phe Thr Asp Asn Ser Ser Pro Pro Ala
1205 1210 1215
Val Pro Gln Thr Phe Gln Val Ala His Leu His Ala Pro Thr Gly
1220 1225 1230
Ser Gly Lys Ser Thr Lys Val Pro Ala Ala Tyr Ala Ala Gln Gly
1235 1240 1245
Tyr Lys Val Leu Val Leu Asn Pro Ser Val Ala Ala Thr Leu Gly
1250 1255 1260
Phe Gly Ala Tyr Met Ser Lys Ala Tyr Gly Val Asp Pro Asn Ile
1265 1270 1275
Arg Thr Gly Val Arg Thr Ile Thr Thr Gly Ala Pro Ile Thr Tyr
1280 1285 1290
Ser Thr Tyr Gly Lys Phe Leu Ala Asp Gly Gly Cys Ser Gly Gly
1295 1300 1305
Ala Tyr Asp Ile Ile Ile Cys Asp Glu Cys His Ser Thr Asp Ser
1310 1315 1320
Thr Ser Ile Leu Gly Ile Gly Thr Val Leu Asp Gln Ala Glu Thr
1325 1330 1335
Ala Gly Ala Arg Leu Val Val Leu Ala Thr Ala Thr Pro Pro Gly
1340 1345 1350
Ser Val Thr Val Pro His Pro Asn Ile Glu Glu Val Ala Leu Ser
1355 1360 1365
Asn Thr Gly Glu Ile Pro Phe Tyr Gly Lys Ala Ile Pro Leu Glu
1370 1375 1380
Val Ile Lys Gly Gly Arg His Leu Ile Phe Cys His Ser Lys Lys
1385 1390 1395
Lys Cys Asp Glu Leu Ala Ala Lys Leu Ser Gly Leu Gly Val Asn
1400 1405 1410
Ala Val Ala Tyr Tyr Arg Gly Leu Asp Val Ser Val Ile Pro Thr
1415 1420 1425
Ser Gly Asp Val Val Val Val Ala Thr Asp Ala Leu Met Thr Gly
1430 1435 1440
Tyr Thr Gly Asp Phe Asp Ser Val Ile Asp Cys Asn Thr Cys Val
1445 1450 1455
Thr Gln Thr Val Asp Phe Ser Leu Asp Pro Thr Phe Thr Ile Glu
1460 1465 1470
Thr Thr Thr Val Pro Gln Asp Ala Val Ser Arg Ser Gln Arg Arg
1475 1480 1485
Gly Arg Thr Gly Arg Gly Arg Gly Gly Ile Tyr Arg Phe Val Thr
1490 1495 1500
Pro Gly Glu Arg Pro Ser Gly Met Phe Asp Ser Ser Val Leu Cys
1505 1510 1515
Glu Cys Tyr Asp Ala Gly Cys Ala Trp Tyr Glu Leu Thr Pro Ala
1520 1525 1530
Glu Thr Ser Val Arg Leu Arg Ala Tyr Leu Asn Thr Pro Gly Leu
1535 1540 1545
Pro Val Cys Gln Asp His Leu Glu Phe Trp Glu Gly Val Phe Thr
1550 1555 1560
Gly Leu Thr His Ile Asp Ala His Phe Leu Ser Gln Thr Lys Gln
1565 1570 1575
Ala Gly Asp Asn Phe Pro Tyr Leu Val Ala Tyr Gln Ala Thr Val
1580 1585 1590
Cys Ala Arg Ala Gln Ala Pro Pro Pro Ser Trp Asp Gln Met Trp
1595 1600 1605
Lys Cys Leu Ile Arg Leu Lys Pro Thr Leu His Gly Pro Thr Pro
1610 1615 1620
Leu Leu Tyr Arg Leu Gly Ala Val Gln Asn Glu Val Thr Leu Thr
1625 1630 1635
His Pro Met Thr Lys Tyr Ile Met Thr Cys Met Ser Ala Asp Leu
1640 1645 1650
Glu Val Val Thr Ser Thr Trp Val Leu Val Gly Gly Val Leu Ala
1655 1660 1665
Ala Leu Ala Ala Tyr Cys Leu Thr Thr Gly Ser Val Val Ile Ile
1670 1675 1680
Gly Arg Ile Ile Leu Ser Gly Arg Pro Ala Ile Ile Pro Asp Arg
1685 1690 1695
Glu Val Leu Tyr Gln Glu Phe Asp Glu Met Glu Glu Cys Ala Ser
1700 1705 1710
His Leu Pro Tyr Ile Glu Gln Gly Met Gln Leu Ala Glu Gln Phe
1715 1720 1725
Lys Gln Lys Ala Leu Gly Leu Leu Gln Thr Ala Thr Lys Gln Ala
1730 1735 1740
Glu Ala Ala Ala Pro Val Val Glu Ser Lys Trp Gln Ala Leu Glu
1745 1750 1755
Ala Phe Trp Ala Lys His Met Trp Asn Phe Ile Ser Gly Ile Gln
1760 1765 1770
Tyr Leu Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Ile Ala
1775 1780 1785
Ser Leu Met Ala Phe Thr Ala Ser Ile Thr Ser Pro Leu Thr Thr
1790 1795 1800
Leu His Thr Leu Leu Phe Asn Ile Leu Gly Gly Trp Val Ala Ala
1805 1810 1815
Gln Leu Ala Pro Pro Ser Ala Ala Ser Ala Phe Val Gly Ala Gly
1820 1825 1830
Ile Ala Gly Ala Ala Val Gly Ser Ile Gly Leu Gly Lys Val Leu
1835 1840 1845
Val Asp Ile Leu Ala Gly Tyr Gly Ala Gly Val Ala Gly Ala Leu
1850 1855 1860
Val Ala Phe Lys Val Met Ser Gly Glu Val Pro Ser Thr Glu Asp
1865 1870 1875
Leu Val Asn Leu Leu Pro Ala Ile Leu Ser Pro Gly Ala Leu Val
1880 1885 1890
Val Gly Val Val Cys Ala Ala Ile Leu Arg Arg His Val Gly Pro
1895 1900 1905
Gly Glu Gly Ala Val Gln Trp Met Asn Arg Leu Ile Ala Phe Ala
1910 1915 1920
Ser Arg Gly Asn His Val Ser Pro Thr His Tyr Val Pro Glu Ser
1925 1930 1935
Asp Ala Ala Ala Arg Val Thr Gln Ile Leu Ser Ser Leu Thr Ile
1940 1945 1950
Thr Gln Leu Leu Lys Arg Leu His Gln Trp Ile Asn Lys Asp Cys
1955 1960 1965
Ser Thr Pro Cys Ser Gly Ser Trp Leu Arg Asp Val Trp Asp Trp
1970 1975 1980
Ile Cys Thr Val Leu Thr Asp Phe Lys Thr Trp Leu Gln Ser Lys
1985 1990 1995
Leu Leu Pro Arg Leu Pro Gly Leu Pro Phe Phe Ser Cys Gln Arg
2000 2005 2010
Gly Tyr Lys Gly Val Trp Leu Gly Asp Gly Val Met Gln Thr Thr
2015 2020 2025
Cys Pro Cys Gly Ala Gln Ile Ser Gly His Val Lys Asn Gly Ser
2030 2035 2040
Met Lys Ile Val Gly Pro Lys Thr Cys Ser Asn Thr Trp His Gly
2045 2050 2055
Thr Phe Pro Ile Asn Ala Tyr Thr Thr Gly Pro Cys Thr Pro Ser
2060 2065 2070
Pro Ala Pro Asn Tyr Ser Lys Ala Leu Trp Arg Val Ala Ala Glu
2075 2080 2085
Glu Tyr Val Glu Val Thr Arg Val Gly Asp Phe His Tyr Val Thr
2090 2095 2100
Gly Met Thr Thr Asp Asn Val Lys Cys Pro Cys Gln Val Pro Ala
2105 2110 2115
Pro Glu Phe Phe Thr Glu Leu Asp Gly Val Arg Leu His Arg Tyr
2120 2125 2130
Ala Pro Ala Cys Lys Pro Leu Leu Arg Asp Glu Val Thr Phe Gln
2135 2140 2145
Val Gly Leu Asn Gln Tyr Pro Val Gly Ser Gln Leu Pro Cys Glu
2150 2155 2160
Pro Glu Pro Asp Val Thr Val Leu Thr Ser Met Leu Thr Asp Pro
2165 2170 2175
Ser His Ile Thr Ala Glu Thr Ala Lys Arg Arg Leu Ala Arg Gly
2180 2185 2190
Ser Pro Pro Ser Leu Ala Ser Ser Ser Ala Ser Gln Leu Ser Ala
2195 2200 2205
Pro Ser Leu Lys Ala Thr Cys Thr Thr His His Asp Ser Pro Asp
2210 2215 2220
Ala Asp Leu Ile Glu Ala Asn Leu Leu Trp Arg Gln Glu Met Gly
2225 2230 2235
Gly Asn Ile Thr Arg Val Glu Ser Glu Asn Lys Val Val Ile Leu
2240 2245 2250
Asp Ser Phe Glu Pro Leu Arg Ala Glu Glu Asp Asp Arg Glu Val
2255 2260 2265
Ser Val Ala Ala Glu Ile Leu Arg Arg Thr Arg Lys Phe Pro Ala
2270 2275 2280
Ala Met Pro Ile Trp Ala Arg Pro Asp Tyr Asn Pro Pro Leu Leu
2285 2290 2295
Glu Ser Trp Lys Asn Pro Asp Tyr Val Pro Pro Val Val His Gly
2300 2305 2310
Cys Pro Leu Pro Pro Ile Lys Ala Pro Pro Ile Pro Pro Pro Arg
2315 2320 2325
Arg Lys Arg Thr Val Ile Leu Thr Glu Ser Thr Val Ser Ser Ala
2330 2335 2340
Leu Ala Glu Leu Ala Thr Lys Thr Phe Gly Ser Ser Gly Ser Ser
2345 2350 2355
Ala Val Asp Ser Gly Thr Ala Thr Gly Pro Pro Asp Gln Ser Ser
2360 2365 2370
Gly Asp Gly Asp Thr Gly Ser Asp Ala Glu Ser Cys Ser Ser Met
2375 2380 2385
Pro Pro Leu Glu Gly Glu Pro Gly Asp Pro Asp Leu Ser Asp Gly
2390 2395 2400
Ser Trp Ser Thr Val Ser Glu Glu Ala Gly Glu Asp Val Val Cys
2405 2410 2415
Cys Ser Met Ser Tyr Thr Trp Thr Gly Ala Leu Ile Thr Pro Cys
2420 2425 2430
Ala Ala Glu Glu Ser Lys Leu Pro Ile Asn Ala Leu Ser Asn Ser
2435 2440 2445
Leu Leu Arg His His Asn Met Val Tyr Ala Thr Thr Ser Arg Ser
2450 2455 2460
Ala Gly Gln Arg Gln Lys Lys Val Thr Phe Asp Arg Val Gln Val
2465 2470 2475
Leu Asp Asp His Tyr Arg Asp Val Leu Lys Glu Met Lys Ala Lys
2480 2485 2490
Ala Ser Thr Val Lys Ala Lys Leu Leu Pro Val Glu Glu Ala Cys
2495 2500 2505
Arg Leu Thr Pro Pro His Ser Ala Arg Ser Lys Phe Gly Tyr Gly
2510 2515 2520
Ala Lys Asp Val Arg Asn Leu Ser Ser Lys Ala Val Asn His Ile
2525 2530 2535
His Ser Val Trp Lys Asp Leu Leu Glu Asp Ser Glu Thr Pro Ile
2540 2545 2550
Asp Thr Thr Ile Met Ala Lys Asn Glu Val Phe Cys Val Gln Pro
2555 2560 2565
Glu Lys Gly Gly Arg Lys Ser Ala Arg Leu Ile Val Phe Pro Asp
2570 2575 2580
Leu Gly Val Arg Val Cys Glu Lys Met Ala Leu Tyr Asp Val Val
2585 2590 2595
Ser Thr Leu Pro Gln Ala Val Met Gly Ser Ser Tyr Gly Phe Gln
2600 2605 2610
Tyr Ser Pro Gly Gln Arg Val Glu Phe Leu Val Asn Ala Trp Lys
2615 2620 2625
Ser Lys Lys Asn Pro Met Gly Phe Ala Tyr Asp Thr Arg Cys Phe
2630 2635 2640
Asp Ser Thr Val Thr Glu Ser Asp Ile Arg Val Glu Glu Ser Ile
2645 2650 2655
Tyr Gln Cys Cys Asp Leu Ala Pro Glu Ala Arg Gln Val Ile Arg
2660 2665 2670
Ser Leu Thr Glu Arg Leu Tyr Ile Gly Gly Pro Leu Thr Asn Ser
2675 2680 2685
Lys Gly Gln Ser Cys Gly Tyr Arg Arg Cys Arg Ala Ser Gly Val
2690 2695 2700
Leu Thr Thr Ser Cys Gly Asn Thr Leu Thr Cys Tyr Leu Lys Ala
2705 2710 2715
Ser Ala Ala Cys Arg Ala Ala Lys Leu Gln Asp Cys Thr Met Leu
2720 2725 2730
Val Cys Gly Asp Asp Leu Val Val Ile Cys Glu Ser Ala Gly Thr
2735 2740 2745
Gln Glu Asp Ala Ala Ser Leu Arg Val Phe Thr Glu Ala Met Thr
2750 2755 2760
Arg Tyr Ser Ala Pro Pro Gly Asp Pro Pro Gln Pro Glu Tyr Asp
2765 2770 2775
Leu Glu Leu Ile Thr Ser Cys Ser Ser Asn Val Ser Val Ala His
2780 2785 2790
Asp Ala Leu Gly Lys Arg Val Tyr Tyr Leu Thr Arg Asp Pro Thr
2795 2800 2805
Thr Pro Leu Ala Arg Ala Ala Trp Glu Thr Ala Arg His Thr Pro
2810 2815 2820
Val Asn Ser Trp Leu Gly Asn Ile Ile Met Tyr Ala Pro Thr Leu
2825 2830 2835
Trp Ala Arg Met Ile Leu Met Thr His Phe Phe Ser Ile Leu Leu
2840 2845 2850
Ala Gln Glu Gln Leu Glu Lys Ala Leu Asp Cys Gln Ile Tyr Gly
2855 2860 2865
Ala Thr Tyr Ser Ile Glu Pro Leu Asp Leu Pro Gln Ile Ile Gln
2870 2875 2880
Arg Leu His Gly Leu Ser Ala Phe Ser Leu His Ser Tyr Ser Pro
2885 2890 2895
Gly Glu Ile Asn Arg Val Ala Ser Cys Leu Arg Lys Leu Gly Val
2900 2905 2910
Pro Pro Leu Arg Val Trp Arg His Arg Ala Arg Ser Val Arg Ala
2915 2920 2925
Lys Leu Leu Ser Gln Gly Gly Arg Ala Ala Thr Cys Gly Lys Tyr
2930 2935 2940
Leu Phe Asn Trp Ala Val Arg Thr Lys Leu Lys Leu Thr Pro Ile
2945 2950 2955
Pro Ala Ala Ser Gln Leu Asp Leu Ser Gly Trp Phe Ile Ala Gly
2960 2965 2970
Tyr Ser Gly Gly Asp Ile Tyr His Ser Leu Ser Arg Ala Arg Pro
2975 2980 2985
Arg Trp Phe Met Trp Cys Leu Leu Leu Leu Ser Val Gly Val Gly
2990 2995 3000
Ile Tyr Leu Leu Pro Asn Arg
3005 3010
<210>65
<211>783
<212>RNA
<213>丙型肝炎病毒
<400>65
gccucacacc uucccuacau cgaacaagga augcagcucg ccgagcaauu caagcagaag 60
gcgcucgggu uguugcaaac ggccaccaag caagcggagg ccgcugcucc cgugguggag 120
uccaaauggc aagcccuuga ggccuucugg gcgaagcaca uguggaacuu caucagcggg 180
auacaguauc uagcaggcuu guccacucug ccuggaaacc ccgcgauagc aucgcugaug 240
gcauuuacag ccucuaucac uagcccgcuc accacccuac auacccuucu auuuaacauc 300
uuggggggau ggguggccgc ccaacucgcc ccccccagcg cugcuucagc cuucguaggc 360
gccggcaucg ccggcgcggc uguuggcagc auaggucuug ggaaggugcu cguggacauc 420
cuagcggguu auggagcagg gguggcaggc gcacucgugg ccuucaaggu caugagcggc 480
gaagugcccu ccacugagga ccuggucaac uuacucccug ccauccucuc cccuggugcc 540
cuggucgucg gggucgugug cgcagcgaua cugcgucggc augugggccc aggggagggg 600
gccgugcagu ggaugaaccg gcugauagcg uucgcuucgc gggguaacca cgucuccccc 660
acgcacuaug ugccugagag cgacgccgca gcgcguguca cccagauccu cuccagccuu 720
accaucacuc agcugcuaaa gaggcuccac caguggauua auaaggacug uuccacgcca 780
ugc 783
<210>66
<211>261
<212>PRT
<213>丙型肝炎病毒
<400>66
Ala Ser His Leu Pro Tyr Ile Glu Gln Gly Met Gln Leu Ala Glu Gln
1 5 10 15
Phe Lys Gln Lys Ala Leu Gly Leu Leu Gln Thr Ala Thr Lys Gln Ala
20 25 30
Glu Ala Ala Ala Pro Val Val Glu Ser Lys Trp Gln Ala Leu Glu Ala
35 40 45
Phe Trp Ala Lys His Met Trp Asn Phe Ile Ser Gly Ile Gln Tyr Leu
50 55 60
Ala Gly Leu Ser Thr Leu Pro Gly Asn Pro Ala Ile Ala Ser Leu Met
65 70 75 80
Ala Phe Thr Ala Ser Ile Thr Ser Pro Leu Thr Thr Leu His Thr Leu
85 90 95
Leu Phe Asn Ile Leu Gly Gly Trp Val Ala Ala Gln Leu Ala Pro Pro
100 105 110
Ser Ala Ala Ser Ala Phe Val Gly Ala Gly Ile Ala Gly Ala Ala Val
115 120 125
Gly Ser Ile Gly Leu Gly Lys Val Leu Val Asp Ile Leu Ala Gly Tyr
130 135 140
Gly Ala Gly Val Ala Gly Ala Leu Val Ala Phe Lys Val Met Ser Gly
145 150 155 160
Glu Val Pro Ser Thr Glu Asp Leu Val Asn Leu Leu Pro Ala Ile Leu
165 170 175
Ser Pro Gly Ala Leu Val Val Gly Val Val Cys Ala Ala Ile Leu Arg
180 185 190
Arg His Val Gly Pro Gly Glu Gly Ala Val Gln Trp Met Asn Arg Leu
195 200 205
Ile Ala Phe Ala Ser Arg Gly Asn His Val Ser Pro Thr His Tyr Val
210 215 220
Pro Glu Ser Asp Ala Ala Ala Arg Val Thr Gln Ile Leu Ser Ser Leu
225 230 235 240
Thr Ile Thr Gln Leu Leu Lys Arg Leu His Gln Trp Ile Asn Lys Asp
245 250 255
Cys Ser Thr Pro Cys
260
<210>67
<211>8010
<212>RNA
<213>人工序列
<220>
<223>亚基因组HCV RNA复制子
<400>67
uaauacgacu cacuauagcc agcccccgau ugggggcgac acuccaccau agaucacucc 60
ccugugagga acuacugucu ucacgcagaa agcgucuagc cauggcguua guaugagugu 120
cgugcagccu ccaggacccc cccucccggg agagccauag uggucugcgg aaccggugag 180
uacaccggaa uugccaggac gaccgggucc uuucuuggau caacccgcuc aaugccugga 240
gauuugggcg ugcccccgcg agacugcuag ccgaguagug uugggucgcg aaaggccuug 300
ugguacugcc ugauagggug cuugcgagug ccccgggagg ucucguagac cgugcaccau 360
gagcacgaau ccuaaaccuc aaagaaaaac caaacguaac accaacgggc gcgccaugau 420
ugaacaagau ggauugcacg cagguucucc ggccgcuugg guggagaggc uauucggcua 480
ugacugggca caacagacaa ucggcugcuc ugaugccgcc guguuccggc ugucagcgca 540
ggggcgcccg guucuuuuug ucaagaccga ccuguccggu gcccugaaug aacugcagga 600
cgaggcagcg cggcuaucgu ggcuggccac gacgggcguu ccuugcgcag cugugcucga 660
cguugucacu gaagcgggaa gggacuggcu gcuauugggc gaagugccgg ggcaggaucu 720
ccugucaucu caccuugcuc cugccgagaa aguauccauc auggcugaug caaugcggcg 780
gcugcauacg cuugauccgg cuaccugccc auucgaccac caagcgaaac aucgcaucga 840
gcgagcacgu acucggaugg aagccggucu ugucgaucag gaugaucugg acgaagagca 900
ucaggggcuc gcgccagccg aacuguucgc caggcucaag gcgcgcaugc ccgacggcga 960
ggaucucguc gugacccaug gcgaugccug cuugccgaau aucauggugg aaaauggccg 1020
cuuuucugga uucaucgacu guggccggcu ggguguggcg gaccgcuauc aggacauagc 1080
guuggcuacc cgugauauug cugaagagcu uggcggcgaa ugggcugacc gcuuccucgu 1140
gcuuuacggu aucgccgcuc ccgauucgca gcgcaucgcc uucuaucgcc uucuugacga 1200
guucuucuga guuuaaacag accacaacgg uuucccucua gcgggaucaa uuccgccccu 1260
cucccucccc ccccccuaac guuacuggcc gaagccgcuu ggaauaaggc cggugugcgu 1320
uugucuauau guuauuuucc accauauugc cgucuuuugg caaugugagg gcccggaaac 1380
cuuggcccug ucuucuugac gagcauuccu aggggucuuu ccccucucgc caaaggaaug 1440
caaggucugu uggaugucgu gaaggaagca guuccucugg gaagcuucuu gaagacaaac 1500
aacgucugua gcgacccuuu gcaggcagcg gaacccccca ccuggcgaca ggugccucug 1560
cggccaaaag ccacguguau aagauacacc ugcaaaggcg guacaacccc agugccacgu 1620
ugugaguugg auaguugugg aaagagucaa auggcucucc ucaagcguau ucaacaaggg 1680
gcugaaggau gcccagaagg uaccccauug uaugggaucu gaucuggggc cucggugcac 1740
augcucuaca uguguuuagu cgagguuaaa aaaacgucua ggccccccga accacgggga 1800
cgugguuuuc cuuugaaaaa cacgauaaua ccauggcgcc caucacggcc uacucccaac 1860
agacgcgggg cuuacuuggc uguaucauca ccggccucac aggucgagac aagaaccagg 1920
ucgaagggga gguucaggug guuuccaccg caacacaguc uuucuuggca accugcguca 1980
acggugugug uuggacuguc uaccauggug ccggcucaaa gacccuagcc ggcccgaagg 2040
ggccaaucac ccagauguac accaacguag accaagaccu cguuggcugg caggcgcccc 2100
ccggggcgcg uuccaugacg ccgugcaccu gcggcagcuc ggaccuuuac uuggucacga 2160
ggcaugcuga ugucauuccg gugcgccggc ggggugacag cagagggagc cuacuuuccc 2220
ccaggcccgu cuccuacuug aagggcucuu cagguggucc acugcucugc cccuuggggc 2280
acgucguggg caucuuucgg gcugccgugu gcacccgggg gguugcgaag gcgguggacu 2340
ucauacccau cgagucuaug gaaacuacca ugcggucucc ggucuuuacg gauaauucau 2400
cucccccggc cguaccgcag acuuuucaag uggcccaucu gcacgccccc acuggcagcg 2460
gcaagagcac caaggugcca gcugcguaug cagcccaggg guacaaggug cuugucuuga 2520
auccauccgu ugccgccacc uuggguuuug gggcguauau guccaaggca uacggugucg 2580
acccuaacau uagaacuggg guaaggacca ucaccacagg cgcucccauc acguacucca 2640
ccuacggcaa guuccuugcc gacggugguu gcuccggggg cgcuuacgac aucauaauau 2700
gcgaugagug ccacucaacc gacucgacuu ccauuuuggg cauuggcacg guccuggauc 2760
aagcggagac ggcuggagcg cgacucgucg ugcucgccac cgcuacgccu ccgggaucgg 2820
ucacugugcc acaccccaac aucgaggagg uggccuuguc caacaccgga gagauucccu 2880
ucuauggcaa agccaucccc cucgagguca ucaagggggg gaggcaucuc auuuucuguc 2940
auucuaagaa gaagugugau gagcucgcug caaagcuguc gggccuuggg gucaacgcug 3000
uagcguacua ccggggucuu gauguguccg ucauaccaac aagcggggac gucguugucg 3060
uggcaacaga cgcucuaaug acgggcuaca ccggugacuu ugacucugug aucgacugua 3120
auacaugugu cacccagaca gucgacuuca gccuggaccc caccuucacc auugagacga 3180
cgaccgugcc ccaagacgca gugucgcgcu cgcagcggcg agggaggacu gguaggggua 3240
gagggggcau auacagguuu gugacuccag gagagcggcc cucgggcaug uucgauuccu 3300
cgguccugug ugaaugcuau gacgcgggcu gugcuuggua cgagcucacg cccgccgaga 3360
ccucgguuag gcugcgggcu uaccuaaaua caccaggguu gcccgucugc caggaccauu 3420
uggaguucug ggaaggcguc uucacaggcc ucacucauau agaugcccac uucuugucuc 3480
agacuaagca ggcaggagac aacuuccccu accugguggc auaccaggcc acagugugcg 3540
ccagggccca ggcaccaccu ccaucauggg aucaaaugug gaagugucuc auacggcuaa 3600
aaccuacacu acacgggcca acaccccugu uguacaggcu aggagccguc caaaacgagg 3660
ucacccucac acaccccaug accaaauaca ucaugacaug caugucggcu gaccuagagg 3720
ucgucaccag cacuugggug cuggugggcg ggguccucgc agcuuuggcc gcguacugcu 3780
ugacaacggg cagcgugguu aucauaggca ggaucaucuu guccggaagg ccggcuauca 3840
uucccgauag ggaaguucuc uaccaggagu ucgaugaaau ggaagagugc gccucacacc 3900
uucccuacau cgaacaagga augcagcucg ccgagcaauu caagcagaag gcgcucgggu 3960
uguugcaaac ggccaccaag caagcggagg ccgcugcucc cgugguggag uccaaauggc 4020
aagcccuuga ggccuucugg gcgaagcaca uguggaacuu caucagcggg auacaguauc 4080
uagcaggcuu guccacucug ccuggaaacc ccgcgauagc aucgcugaug gcauuuacag 4140
ccucuaucac uagcccgcuc accacccuac auacccuucu auuuaacauc uuggggggau 4200
ggguggccgc ccaacucgcc ccccccagcg cugcuucagc cuucguaggc gccggcaucg 4260
ccggcgcggc uguuggcagc auaggucuug ggaaggugcu cguggacauc cuagcggguu 4320
auggagcagg gguggcaggc gcacucgugg ccuucaaggu caugagcggc gaagugcccu 4380
ccacugagga ccuggucaac uuacucccug ccauccucuc cccuggugcc cuggucgucg 4440
gggucgugug cgcagcgaua cugcgucggc augugggccc aggggagggg gccgugcagu 4500
ggaugaaccg gcugauagcg uucgcuucgc gggguaacca cgucuccccc acgcacuaug 4560
ugccugagag cgacgccgca gcgcguguca cccagauccu cuccagccuu accaucacuc 4620
agcugcuaaa gaggcuccac caguggauua auaaggacug uuccacgcca ugcuccgguu 4680
cguggcucag ggauguuugg gacuggauau gcacgguuuu gaccgacuuc aaaaccuggc 4740
uccaguccaa gcuccugcca cgguugccgg gacucccuuu cuuuucaugu caacguggau 4800
auaaaggagu cuggcuggga gauggcguua ugcaaacuac cuguccaugu ggugcacaaa 4860
ucagcggaca ugucaaaaac ggcuccauga agaucguggg gccuaaaacc ugcagcaaca 4920
cguggcacgg gacguucccc aucaacgcau acaccacagg ccccugcaca cccuccccgg 4980
cgccgaacua uuccaaggcg uuguggcgag uggcugcuga ggaguaugug gaggucacgc 5040
ggguggggga uuuccacuac gugacgggca ugaccacuga caacguaaaa ugcccaugcc 5100
aggucccggc ccccgaauuc uucacggagu uggauggggu gcggcugcac agguacgcuc 5160
cggcgugcaa gccucucuua cgggaugagg ucacauucca ggucgggcuc aaccaguauc 5220
cgguuggauc acagcuucca ugugagcccg agccggaugu aacagugcuc acuuccaugc 5280
ucaccgaccc cucccauauu acagcagaga cggcuaagcg uaggcuggcc agaggguccc 5340
cccccucuuu ggccagcucc ucagcuagcc aguugucugc gccuuccuug aaggcgacau 5400
gcacuaccca ccaugacucc ccagaugcug accucaucga ggccaaccuc cuguggcggc 5460
aggagauggg cgggaacauc acccgcgugg agucagagaa caagguagua auucuggacu 5520
cuuuugaacc gcuucgagcg gaggaggaug auagggaagu guccguagcg gcggagaucc 5580
ugcggagaac caggaaauuc cccgcagcga ugcccauaug ggcacggccg gacuacaacc 5640
caccacuccu agagucuugg aagaacccag acuacguccc uccaguggua cacgggugcc 5700
cauuaccacc uauuaaggcc ccuccgauac caccuccacg gagaaagagg acggucaucc 5760
ugacagaauc caccgugucu ucugccuugg cggagcuugc uacaaagacc uuuggcagcu 5820
ccggaucguc ggccguugac agcggcacag cgacuggccc uccugaucag uccuccggug 5880
acggagauac aggauccgac gcugagucgu gcuccuccau gcccccccuu gagggggagc 5940
cgggggaccc cgaucucagc gacgggucuu ggucuaccgu gagcgaggag gccggugagg 6000
acgucgucug cugcucgaug uccuacacau ggacaggcgc cuuaaucaca ccgugcgccg 6060
cagaggagag caagcugccu aucaacgcgu ugagcaacuc uuugcugcgc caccacaaca 6120
uggucuaugc cacaacaucc cgcagcgcgg gccaacggca gaagaagguc acuuuugaca 6180
gagugcaggu ccuggacgac cauuaccggg acgugcucaa ggagaugaag gcgaaggcgu 6240
ccacaguuaa ggcuaaacuu cuaccuguag aagaagccug caggcugacg cccccacacu 6300
cggccagauc caaguuuggc uauggggcga aggacguccg gaaccuaucc agcaaggccg 6360
ucaaccacau ccacuccgug uggaaggacu ugcuggaaga cucugagacg ccgauugaca 6420
ccaccaucau ggcaaaaaau gaggucuuuu guguucaacc agagaaagga ggccgcaagu 6480
cagcucgucu uaucguauuc ccagacuugg ggguucgugu gugcgagaaa auggcccuuu 6540
acgacguggu uuccacucuu ccucaggccg ugaugggcuc cucauacggg uuccaguacu 6600
cuccuggaca gcgggucgag uuccugguga augccuggaa aucaaagaag aacccuaugg 6660
gcuucgcaua ugacacccgc uguuuugacu caacggucac ugagagugac auccguguug 6720
aggagucaau uuaccaaugu ugugacuugg cccccgaggc cagacagguc auaaggucgc 6780
ucacggagcg gcuuuauauc gggggccccc ugacuaauuc aaaagggcag agcugcggcu 6840
aucgccggug ccgcgccagc ggugugcuga cgaccagcug cgguaauacc cucacauguu 6900
acuugaaggc uucugcagcc ugucgagcug caaagcucca ggacugcaca auguuagugu 6960
gcggagacga ccuugucguu aucugugaaa gugcgggaac ccaggaggac gcggcgagcc 7020
uacgagucuu cacggaggcu augacuaggu acucugcccc ccccggggac ccgccccagc 7080
cagaauacga cuuggagcug auaacaucau gcuccuccaa cgucucgguc gcgcacgaug 7140
cacuuggcaa gcggguguau uaucugaccc gcgaccccac caccccccuu gcgcgggcug 7200
cgugggagac agcaagacac acuccaguua acuccuggcu aggcaacauc aucauguaug 7260
cgcccacccu augggcaagg augauucuga ugacccacuu cuuuuccauc cuucuagcuc 7320
aggaacaacu ugaaaaagcc cuagauuguc agaucuacgg ggccacuuac uccauugagc 7380
cacuugaccu accucagauc auucagcgac uccacggccu uagcgcauuu ucacuccaua 7440
gcuacucucc aggugagauc aauagggugg cuucaugccu caggaaacuu gggguaccac 7500
ccuugcgagu cuggagacau cgggccagaa guguccgcgc uaagcuacug ucccaggggg 7560
ggagggccgc cacuuguggc aaauaccucu ucaacugggc aguaaggacc aagcucaaac 7620
ucacuccaau uccggcugcg ucccaguugg acuuguccgg cugguucauu gcugguuaca 7680
gcgggggaga cauauaucac agccugucuc gcgcccgacc ccgcugguuc auguggugcc 7740
uacuccuacu uuccguaggg guaggcaucu aucugcuccc caaucgauga acggggggcu 7800
aaacacucca ggccaauagg ccauucuguu uuuuuuuuuu uuuuuuuuuu uuuuuuuuuu 7860
uuuuuuuuuu uuuuuuuuuu uuccuuuuuu uuuuuuuuuu ucccuuucuu uugguggcuc 7920
caucuuagcc cuagucacgg cuagcuguga aagguccgug agccgcauga cugcagagag 7980
ugcugauacu ggccucucug cagaucaugu 8010
<210>68
<211>8010
<212>RNA
<213>人工序列
<220>
<223>亚基因组HCV RNA复制子
<400>68
uaauacgacu cacuauagcc agcccccgau ugggggcgac acuccaccau agaucacucc 60
ccugugagga acuacugucu ucacgcagaa agcgucuagc cauggcguua guaugagugu 120
cgugcagccu ccaggacccc cccucccggg agagccauag uggucugcgg aaccggugag 180
uacaccggaa uugccaggac gaccgggucc uuucuuggau caacccgcuc aaugccugga 240
gauuugggcg ugcccccgcg agacugcuag ccgaguagug uugggucgcg aaaggccuug 300
ugguacugcc ugauagggug cuugcgagug ccccgggagg ucucguagac cgugcaccau 360
gagcacgaau ccuaaaccuc aaagaaaaac caaacguaac accaacgggc gcgccaugau 420
ugaacaagau ggauugcacg cagguucucc ggccgcuugg guggagaggc uauucggcua 480
ugacugggca caacagacaa ucggcugcuc ugaugccgcc guguuccggc ugucagcgca 540
ggggcgcccg guucuuuuug ucaagaccga ccuguccggu gcccugaaug aacugcagga 600
cgaggcagcg cggcuaucgu ggcuggccac gacgggcguu ccuugcgcag cugugcucga 660
cguugucacu gaagcgggaa gggacuggcu gcuauugggc gaagugccgg ggcaggaucu 720
ccugucaucu caccuugcuc cugccgagaa aguauccauc auggcugaug caaugcggcg 780
gcugcauacg cuugauccgg cuaccugccc auucgaccac caagcgaaac aucgcaucga 840
gcgagcacgu acucggaugg aagccggucu ugucgaucag gaugaucugg acgaagagca 900
ucaggggcuc gcgccagccg aacuguucgc caggcucaag gcgcgcaugc ccgacggcga 960
ggaucucguc gugacccaug gcgaugccug cuugccgaau aucauggugg aaaauggccg 1020
cuuuucugga uucaucgacu guggccggcu ggguguggcg gaccgcuauc aggacauagc 1080
guuggcuacc cgugauauug cugaagagcu uggcggcgaa ugggcugacc gcuuccucgu 1140
gcuuuacggu aucgccgcuc ccgauucgca gcgcaucgcc uucuaucgcc uucuugacga 1200
guucuucuga guuuaaacag accacaacgg uuucccucua gcgggaucaa uuccgccccu 1260
cucccucccc ccccccuaac guuacuggcc gaagccgcuu ggaauaaggc cggugugcgu 1320
uugucuauau guuauuuucc accauauugc cgucuuuugg caaugugagg gcccggaaac 1380
cuuggcccug ucuucuugac gagcauuccu aggggucuuu ccccucucgc caaaggaaug 1440
caaggucugu uggaugucgu gaaggaagca guuccucugg gaagcuucuu gaagacaaac 1500
aacgucugua gcgacccuuu gcaggcagcg gaacccccca ccuggcgaca ggugccucug 1560
cggccaaaag ccacguguau aagauacacc ugcaaaggcg guacaacccc agugccacgu 1620
ugugaguugg auaguugugg aaagagucaa auggcucucc ucaagcguau ucaacaaggg 1680
gcugaaggau gcccagaagg uaccccauug uaugggaucu gaucuggggc cucggugcac 1740
augcucuaca uguguuuagu cgagguuaaa aaaacgucua ggccccccga accacgggga 1800
cgugguuuuc cuuugaaaaa cacgauaaua ccauggcgcc caucacggcc uacucccaac 1860
agacgcgggg cuuacuuggc uguaucauca ccggccucac aggucgagac aagaaccagg 1920
ucgaagggga gguucaggug guuuccaccg caacacaguc uuucuuggca accugcguca 1980
acggugugug uuggacuguc uaccauggug ccggcucaaa gacccuagcc ggcccgaagg 2040
ggccaaucac ccagauguac accaacguag accaagaccu cguuggcugg caggcgcccc 2100
ucggggcgcg uuccaugacg ccgugcaccu gcggcagcuc ggaccuuuac uuggucacga 2160
ggcaugcuga ugucauuccg gugcgccggc ggggugacag cagagggagc cuacuuuccc 2220
ccaggcccgu cuccuacuug aagggcucuu cagguggucc acugcucugc cccuuggggc 2280
acgucguggg caucuuucgg gcugccgugu gcacccgggg gguugcgaag gcgguggacu 2340
ucauacccau cgagucuaug gaaacuacca ugcggucucc ggucuuuacg gauaauucau 2400
cucccccggc cguaccgcag acuuuucaag uggcccaucu gcacgccccc acuggcagcg 2460
gcaagagcac caaggugcca gcugcguaug cagcccaggg guacaaggug cuugucuuga 2520
auccauccgu ugccgccacc uuggguuuug gggcguauau guccaaggca uacggugucg 2580
acccuaacau uagaacuggg guaaggacca ucaccacagg cgcucccauc acguacucca 2640
ccuacggcaa guuccuugcc gacggugguu gcuccggggg cgcuuacgac aucauaauau 2700
gcgaugagug ccacucaacc gacucgacuu ccauuuuggg cauuggcacg guccuggauc 2760
aagcggagac ggcuggagcg cgacucgucg ugcucgccac cgcuacgccu ccgggaucgg 2820
ucacugugcc acaccccaac aucgaggagg uggccuuguc caacaccgga gagauucccu 2880
ucuauggcaa agccaucccc cucgagguca ucaagggggg gaggcaucuc auuuucuguc 2940
auucuaagaa gaagugugau gagcucgcug caaagcuguc gggccuuggg gucaacgcug 3000
uagcguacua ccggggucuu gauguguccg ucauaccaac aagcggggac gucguugucg 3060
uggcaacaga cgcucuaaug acgggcuaca ccggugacuu ugacucugug aucgacugua 3120
auacaugugu cacccagaca gucgacuuca gccuggaccc caccuucacc auugagacga 3180
cgaccgugcc ccaagacgca gugucgcgcu cgcagcggcg agggaggacu gguaggggua 3240
gagggggcau auacagguuu gugacuccag gagagcggcc cucgggcaug uucgauuccu 3300
cgguccugug ugaaugcuau gacgcgggcu gugcuuggua cgagcucacg cccgccgaga 3360
ccucgguuag gcugcgggcu uaccuaaaua caccaggguu gcccgucugc caggaccauu 3420
uggaguucug ggaaggcguc uucacaggcc ucacucauau agaugcccac uucuugucuc 3480
agacuaagca ggcaggagac aacuuccccu accugguggc auaccaggcc acagugugcg 3540
ccagggccca ggcaccaccu ccaucauggg aucaaaugug gaagugucuc auacggcuaa 3600
aaccuacacu acacgggcca acaccccugu uguacaggcu aggagccguc caaaacgagg 3660
ucacccucac acaccccaug accaaauaca ucaugacaug caugucggcu gaccuagagg 3720
ucgucaccag cacuugggug cuggugggcg ggguccucgc agcuuuggcc gcguacugcu 3780
ugacaacggg cagcgugguu aucauaggca ggaucaucuu guccggaagg ccggcuauca 3840
uucccgauag ggaaguucuc uaccaggagu ucgaugaaau ggaagagugc gccucacacc 3900
uucccuacau cgaacaagga augcagcucg ccgagcaauu caagcagaag gcgcucgggu 3960
uguugcaaac ggccaccaag caagcggagg ccgcugcucc cgugguggag uccaaauggc 4020
aagcccuuga ggccuucugg gcgaagcaca uguggaacuu caucagcggg auacaguauc 4080
uagcaggcuu guccacucug ccuggaaacc ccgcgauagc aucgcugaug gcauuuacag 4140
ccucuaucac uagcccgcuc accacccuac auacccuucu auuuaacauc uuggggggau 4200
ggguggccgc ccaacucgcc ccccccagcg cugcuucagc cuucguaggc gccggcaucg 4260
ccggcgcggc uguuggcagc auaggucuug ggaaggugcu cguggacauc cuagcggguu 4320
auggagcagg gguggcaggc gcacucgugg ccuucaaggu caugagcggc gaagugcccu 4380
ccacugagga ccuggucaac uuacucccug ccauccucuc cccuggugcc cuggucgucg 4440
gggucgugug cgcagcgaua cugcgucggc augugggccc aggggagggg gccgugcagu 4500
ggaugaaccg gcugauagcg uucgcuucgc gggguaacca cgucuccccc acgcacuaug 4560
ugccugagag cgacgccgca gcgcguguca cccagauccu cuccagccuu accaucacuc 4620
agcugcuaaa gaggcuccac caguggauua auaaggacug uuccacgcca ugcuccgguu 4680
cguggcucag ggauguuugg gacuggauau gcacgguuuu gaccgacuuc aaaaccuggc 4740
uccaguccaa gcuccugcca cgguugccgg gacucccuuu cuuuucaugu caacguggau 4800
auaaaggagu cuggcuggga gauggcguua ugcaaacuac cuguccaugu ggugcacaaa 4860
ucagcggaca ugucaaaaac ggcuccauga agaucguggg gccuaaaacc ugcagcaaca 4920
cguggcacgg gacguucccc aucaacgcau acaccacagg ccccugcaca cccuccccgg 4980
cgccgaacua uuccaaggcg uuguggcgag uggcugcuga ggaguaugug gaggucacgc 5040
ggguggggga uuuccacuac gugacgggca ugaccacuga caacguaaaa ugcccaugcc 5100
aggucccggc ccccgaauuc uucacggagu uggauggggu gcggcugcac agguacgcuc 5160
cggcgugcaa gccucucuua cgggaugagg ucacauucca ggucgggcuc aaccaguauc 5220
cgguuggauc acagcuucca ugugagcccg agccggaugu aacagugcuc acuuccaugc 5280
ucaccgaccc cucccauauu acagcagaga cggcuaagcg uaggcuggcc agaggguccc 5340
cccccucuuu ggccagcucc ucagcuagcc aguugucugc gccuuccuug aaggcgacau 5400
gcacuaccca ccaugacucc ccagaugcug accucaucga ggccaaccuc cuguggcggc 5460
aggagauggg cgggaacauc acccgcgugg agucagagaa caagguagua auucuggacu 5520
cuuuugaacc gcuucgagcg gaggaggaug auagggaagu guccguagcg gcggagaucc 5580
ugcggagaac caggaaauuc cccgcagcga ugcccauaug ggcacggccg gacuacaacc 5640
caccacuccu agagucuugg aagaacccag acuacguccc uccaguggua cacgggugcc 5700
cauuaccacc uauuaaggcc ccuccgauac caccuccacg gagaaagagg acggucaucc 5760
ugacagaauc caccgugucu ucugccuugg cggagcuugc uacaaagacc uuuggcagcu 5820
ccggaucguc ggccguugac agcggcacag cgacuggccc uccugaucag uccuccggug 5880
acggagauac aggauccgac gcugagucgu gcuccuccau gcccccccuu gagggggagc 5940
cgggggaccc cgaucucagc gacgggucuu ggucuaccgu gagcgaggag gccggugagg 6000
acgucgucug cugcucgaug uccuacacau ggacaggcgc cuuaaucaca ccgugcgccg 6060
cagaggagag caagcugccu aucaacgcgu ugagcaacuc uuugcugcgc caccacaaca 6120
uggucuaugc cacaacaucc cgcagcgcgg gccaacggca gaagaagguc acuuuugaca 6180
gagugcaggu ccuggacgac cauuaccggg acgugcucaa ggagaugaag gcgaaggcgu 6240
ccacaguuaa ggcuaaacuu cuaccuguag aagaagccug caggcugacg cccccacacu 6300
cggccagauc caaguuuggc uauggggcga aggacguccg gaaccuaucc agcaaggccg 6360
ucaaccacau ccacuccgug uggaaggacu ugcuggaaga cucugagacg ccgauugaca 6420
ccaccaucau ggcaaaaaau gaggucuuuu guguucaacc agagaaagga ggccgcaagu 6480
cagcucgucu uaucguauuc ccagacuugg ggguucgugu gugcgagaaa auggcccuuu 6540
acgacguggu uuccacucuu ccucaggccg ugaugggcuc cucauacggg uuccaguacu 6600
cuccuggaca gcgggucgag uuccugguga augccuggaa aucaaagaag aacccuaugg 6660
gcuucgcaua ugacacccgc uguuuugacu caacggucac ugagagugac auccguguug 6720
aggagucaau uuaccaaugu ugugacuugg cccccgaggc cagacagguc auaaggucgc 6780
ucacggagcg gcuuuauauc gggggccccc ugacuaauuc aaaagggcag agcugcggcu 6840
aucgccggug ccgcgccagc ggugugcuga cgaccagcug cgguaauacc cucacauguu 6900
acuugaaggc uucugcagcc ugucgagcug caaagcucca ggacugcaca auguuagugu 6960
gcggagacga ccuugucguu aucugugaaa gugcgggaac ccaggaggac gcggcgagcc 7020
uacgagucuu cacggaggcu augacuaggu acucugcccc ccccggggac ccgccccagc 7080
cagaauacga cuuggagcug auaacaucau gcuccuccaa cgucucgguc gcgcacgaug 7140
cacuuggcaa gcggguguau uaucugaccc gcgaccccac caccccccuu gcgcgggcug 7200
cgugggagac agcaagacac acuccaguua acuccuggcu aggcaacauc aucauguaug 7260
cgcccacccu augggcaagg augauucuga ugacccacuu cuuuuccauc cuucuagcuc 7320
aggaacaacu ugaaaaagcc cuagauuguc agaucuacgg ggccacuuac uccauugagc 7380
cacuugaccu accucagauc auucagcgac uccacggccu uagcgcauuu ucacuccaua 7440
gcuacucucc aggugagauc aauagggugg cuucaugccu caggaaacuu gggguaccac 7500
ccuugcgagu cuggagacau cgggccagaa guguccgcgc uaagcuacug ucccaggggg 7560
ggagggccgc cacuuguggc aaauaccucu ucaacugggc aguaaggacc aagcucaaac 7620
ucacuccaau uccggcugcg ucccaguugg acuuguccgg cugguucauu gcugguuaca 7680
gcgggggaga cauauaucac agccugucuc gcgcccgacc ccgcugguuc auguggugcc 7740
uacuccuacu uuccguaggg guaggcaucu aucugcuccc caaucgauga acggggggcu 7800
aaacacucca ggccaauagg ccauucuguu uuuuuuuuuu uuuuuuuuuu uuuuuuuuuu 7860
uuuuuuuuuu uuuuuuuuuu uuccuuuuuu uuuuuuuuuu ucccuuucuu uugguggcuc 7920
caucuuagcc cuagucacgg cuagcuguga aagguccgug agccgcauga cugcagagag 7980
ugcugauacu ggccucucug cagaucaugu 8010
Claims (24)
1.丙型肝炎病毒基因，该基因包括选自下述(A)～(F)的多核苷酸：
(A)包含SEQ ID NO：5所示的核苷酸序列的多核苷酸；
(B)包含SEQ ID NO：7所示的核苷酸序列的多核苷酸；
(C)包含SEQ ID NO：65所示的核苷酸序列的多核苷酸；
(D)编码包含SEQ ID NO：6所示的氨基酸序列的多肽的多核苷酸；
(E)编码包含SEQ ID NO：8所示的氨基酸序列的多肽的多核苷酸；以及
(F)编码包含SEQ ID NO：66所示的氨基酸序列的多肽的多核苷酸。
2.权利要求1所述的丙型肝炎病毒基因，该基因为包含SEQ ID NO：1、SEQ ID NO：3、SEQ ID NO：10、SEQ ID NO：61或SEQ ID NO：63所示的核苷酸序列的多核苷酸。
3.基因型1b的丙型肝炎病毒基因，该基因包括编码丙型肝炎病毒的多蛋白的氨基酸序列中第1804位的亮氨酸和第1966位的赖氨酸的核苷酸和编码NS4B蛋白的多核苷酸。
4.DNA，该DNA包括在包含上述权利要求1～3中任一项所述的丙型肝炎病毒基因的核苷酸序列中尿苷置换成胸腺嘧啶的核苷酸序列的单链DNA。
5.多肽，该多肽包含SEQ ID NO：6、SEQ ID NO：8或SEQ ID NO：66所示的氨基酸序列。
6.丙型肝炎病毒多蛋白，其中NS4B区的肽为包含SEQ ID NO：6、SEQ ID NO：8或SEQ ID NO：66所示的氨基酸序列的多肽。
7.丙型肝炎病毒蛋白，该蛋白为：选自包含SEQ ID NO：2、SEQID NO：4、SEQ ID NO：11、SEQ ID NO：62或SEQ ID NO：64所示的氨基酸序列中第1位～第191位氨基酸序列的核心蛋白、包含第192位～第383位氨基酸序列的E1蛋白、包含第384位～第746位氨基酸序列的E2蛋白、包含第747位～第809位氨基酸序列的P7蛋白、包含第810位～第1026位氨基酸序列的NS2蛋白、包含第1027位～第1657位氨基酸序列的NS3蛋白、包含第1658位～第1711位氨基酸序列的NS4A蛋白、包含第1712位～第1972位氨基酸序列的NS4B蛋白、包含第1973位～第2419位氨基酸序列的NS5A蛋白、包含第2420位～第3010位氨基酸序列的NS5B蛋白中的至少一种。
8.复制子RNA，该复制子RNA包括选自下述(A)～(G)的多核苷酸：
(A)包含SEQ ID NO：5所示的核苷酸序列的多核苷酸；
(B)包含SEQ ID NO：7所示的核苷酸序列的多核苷酸；
(C)包含SEQ ID NO：65所示的核苷酸序列的多核苷酸；
(D)编码包含SEQ ID NO：6所示的氨基酸序列的多肽的多核苷酸；
(E)编码包含SEQ ID NO：8所示的氨基酸序列的多肽的多核苷酸；
(F)编码包含SEQ ID NO：66所示的氨基酸序列的多肽的多核苷酸；以及
(G)包含与SEQ ID NO：5、SEQ ID NO：7或SEQ ID NO：65所示的核苷酸序列的同源性为90％以上的核苷酸序列的多核苷酸。
9.基因型1b的复制子RNA，该复制子RNA包括：编码丙型肝炎病毒的多蛋白的氨基酸序列中第1804位的亮氨酸和第1966位的赖氨酸的核苷酸；以及编码NS4B蛋白的多核苷酸。
10.权利要求8或9所述的复制子RNA，该复制子RNA包括：
(A)丙型肝炎病毒的5’非翻译区的第1位～第341位的多核苷酸、编码丙型肝炎病毒的多蛋白中第1027位～第3010位多肽的多核苷酸、以及3’非翻译区的多核苷酸；或
(B)5’非翻译区的第1位～第341位的多核苷酸、编码包含3010个氨基酸的丙型肝炎病毒的多蛋白的多核苷酸、以及3’非翻译区的多核苷酸。
11.权利要求8～10中任一项所述的复制子RNA，该复制子RNA为干扰素抵抗性。
12.权利要求8～11中任一项所述的复制子RNA，该复制子RNA包括：
(A)包含SEQ ID NO：1所示的核苷酸序列中第1位～第341位的核苷酸序列的多核苷酸、以及包含SEQ ID NO：1所示的核苷酸序列中第3420位～第9594位的核苷酸序列的多核苷酸；
(B)包含SEQ ID NO：3所示的核苷酸序列中第1位～第341位的核苷酸序列的多核苷酸、以及包含SEQ ID NO：3所示的核苷酸序列中第3420位～第9594位的核苷酸序列的多核苷酸；
(C)包含SEQ ID NO：10所示的核苷酸序列中第1位～第341位的核苷酸序列的多核苷酸、以及包含SEQ ID NO：10所示的核苷酸序列中第3420位～第9594位的核苷酸序列的多核苷酸；
(D)包含SEQ ID NO：61所示的核苷酸序列中第1位～第341位的核苷酸序列的多核苷酸、以及包含SEQ ID NO：61所示的核苷酸序列中第3420位～第9594位的核苷酸序列的多核苷酸；
(E)包含SEQ ID NO：63所示的核苷酸序列中第1位～第341位的核苷酸序列的多核苷酸、以及包含SEQ ID NO：63所示的核苷酸序列中第3420位～第9594位的核苷酸序列的多核苷酸；
(F)包含相对于SEQ ID NO：1所示的核苷酸序列中第1位～第341位的核苷酸序列为90％以上的同源性的核苷酸序列的多核苷酸、以及包含与SEQ ID NO：1所示的核苷酸序列中第3420位～第9594位的核苷酸序列的同源性为90％以上的核苷酸序列的多核苷酸；
(G)包含相对于SEQ ID NO：3所示的核苷酸序列中第1位～第341位的核苷酸序列为90％以上的同源性的核苷酸序列的多核苷酸、以及包含与SEQ ID NO：3所示的核苷酸序列中第3420位～第9594位的核苷酸序列的同源性为90％以上的核苷酸序列的多核苷酸；
(H)包含相对于SEQ ID NO：10所示的核苷酸序列中第1位～第341位的核苷酸序列为90％以上的同源性的核苷酸序列的多核苷酸、以及包含与SEQ ID NO：10所示的核苷酸序列中第3420位～第9594位的核苷酸序列的同源性为90％以上的核苷酸序列的多核苷酸；
(I)包含相对于SEQ ID NO：61所示的核苷酸序列中第1位～第341位的核苷酸序列为90％以上的同源性的核苷酸序列的多核苷酸、以及包含与SEQ ID NO：61所示的核苷酸序列中第3420位～第9594位的核苷酸序列的同源性为90％以上的核苷酸序列的多核苷酸；或
(J)包含相对于SEQ ID NO：63所示的核苷酸序列中第1位～第341位的核苷酸序列为90％以上的同源性的核苷酸序列的多核苷酸、以及包含与SEQ ID NO：63所示的核苷酸序列中第3420位～第9594位的核苷酸序列的同源性为90％以上的核苷酸序列的多核苷酸。
13.权利要求8～12中任一项所述的复制子RNA，其中上述复制子RNA为：包含SEQ ID NO：1、SEQ ID NO：3、SEQ ID NO：10、SEQ IDNO：61或SEQ ID NO：63所示的核苷酸序列的多核苷酸；或者包含与SEQ ID NO：1、SEQ ID NO：3、SEQ ID NO：10、SEQ ID NO：61或SEQID NO：63所示的核苷酸序列的同源性为90％以上的核苷酸序列的多核苷酸。
14.权利要求8～13中任一项所述的复制子RNA，该复制子RNA包括至少一个选择标记基因或报道基因和至少一个IRES序列。
15.DNA，该DNA编码权利要求8～14中任一项所述的复制子RNA。
16.载体，该载体包括权利要求15所述的DNA。
17.复制子复制细胞，该复制子复制细胞是通过将选自权利要求8～14中任一项所述的复制子RNA、权利要求15所述的DNA和权利要求16所述的载体的至少一种导入到细胞中而制作的。
18.权利要求17所述的复制子复制细胞，其中上述细胞为来自肝细胞的细胞。
19.权利要求18所述的复制子复制细胞，其中上述来自肝细胞的细胞为Huh-7细胞。
20.复制子RNA，该复制子RNA是由权利要求17～19中任一项所述的复制子复制细胞产生的。
21.丙型肝炎病毒蛋白，该蛋白为选自由权利要求17～19中任一项所述的复制子复制细胞产生的CORE、E1、E2、P7、NS2、NS3、NS4A、NS4B、NS5A和NS5B中的至少一种。
22.丙型肝炎病毒颗粒，该颗粒是由权利要求17～19中任一项所述的复制子复制细胞产生的。
23.筛选方法，该筛选方法是筛选控制丙型肝炎病毒感染的物质的方法，该方法包括：使权利要求17～19中任一项所述的复制子复制细胞与上述物质接触的步骤；以及分析复制子RNA的增加度的步骤。
24.权利要求23所述的筛选方法，其中上述分析复制子RNA增加度是指检测复制子RNA或丙型肝炎病毒蛋白。
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| US8834893B2 (en) * | 2008-12-26 | 2014-09-16 | Toray Industries, Inc. | Nucleic acid derived from hepatitis C virus and expression vector, transformed cell, and hepatitis C virus particles each prepared by using the same |
| NZ594155A (en) * | 2009-01-21 | 2013-02-22 | Vertex Pharma | Methods for amplifying hepatitis c virus nucleic acids |
| CA2813675A1 (en) * | 2010-10-08 | 2012-04-12 | Advanced Life Science Institute, Inc. | Hepatitis c virus gene |
| WO2012133735A1 (ja) * | 2011-03-31 | 2012-10-04 | 国立感染症研究所長が代表する日本国 | 遺伝子型１ｂのＣ型肝炎ウイルスゲノム由来の核酸を含む核酸構築物、及び該核酸構築物が導入されたＣ型肝炎ウイルスゲノム複製細胞、並びに感染性Ｃ型肝炎ウイルス粒子の製造方法 |
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| US6582908B2 (en) * | 1990-12-06 | 2003-06-24 | Affymetrix, Inc. | Oligonucleotides |
| US5474796A (en) * | 1991-09-04 | 1995-12-12 | Protogene Laboratories, Inc. | Method and apparatus for conducting an array of chemical reactions on a support surface |
| JPH08187097A (ja) | 1994-12-28 | 1996-07-23 | Tonen Corp | Ｒｎａウィルスのプラス鎖又はマイナス鎖遺伝子の特異的検出方法 |
| ES2373642T3 (es) * | 2000-05-23 | 2012-02-07 | Washington University | Variantes de vhc. |
| JP4880116B2 (ja) | 2000-12-01 | 2012-02-22 | 財団法人 東京都医学総合研究所 | 劇症ｃ型肝炎ウイルス株の遺伝子 |
| DK1694694T3 (da) * | 2003-12-01 | 2013-05-06 | Univ Texas | Replikationskompetent hepatitis C-virus samt anvendelsesfremgangsmåder |
| US8454973B2 (en) * | 2004-08-24 | 2013-06-04 | Tokyo Metropolitan Institute Of Medical Science | Modified human hepatitis C virus genomic RNA that can be autonomously replicated |
| US8168771B2 (en) * | 2005-01-31 | 2012-05-01 | The Johns Hopkins University | Use of consensus sequence as vaccine antigen to enhance recognition of virulent viral variants |
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| CA2692815A1 (en) | 2008-11-13 |
| EP2151495A1 (en) | 2010-02-10 |
| WO2008136470A1 (ja) | 2008-11-13 |
| EP2711427A1 (en) | 2014-03-26 |
| CN102888413A (zh) | 2013-01-23 |
| AU2008246622A1 (en) | 2008-11-13 |
| EP2151495A4 (en) | 2010-06-02 |
| JP2013198486A (ja) | 2013-10-03 |
| US20100173298A1 (en) | 2010-07-08 |
| AU2008246622B2 (en) | 2013-09-26 |
| JPWO2008136470A1 (ja) | 2010-07-29 |
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