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Research of genetic analysis. of hepatitis C virus clones and immune response in reinfection experiment using chimpanzees.

遗传分析研究。

基本信息

批准号：
14570203
负责人：
SUGITANI Masahiko
金额：
$ 1.73万
依托单位：
Nihon University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570203/
关键词：
Hepatitis C virus (HCV)Hypervariable region-1 Chimpanzee Reinfection experiment HCV cloning Anti-HCV antibody hepatitis C virus chimpanzee HCV genotype

项目摘要

To investigate whether the genetically same hepatitis C virus (HCV) could twice reinfect the same chimpanzee or not, we analyzed amino acid sequences of hypervariable region 1 (HVR1) of I-IC V and immune response in a chimpanzee model. Chimpanzees #63 and #65 were inoculated, three times, with sera containing HCV derived from HCV-F strain. After each inoculation, both chimpanzees 4eveloped acute hepatitis C with viremia, then recovered, with the disappearance of HCV RNA. The interval between subsequent inoculations was at least one year after the disappearance of HCV RNA associated with the initial inoculation. Cloning using each inocula as well as each post inoculation acute phase sera of the chimpanzees, sequence and amino acid analysis were performed. Antibody titers against HCV non-structure, core and HVR1 regions were measured. Clones from the first inocula could be divided into major (83%) and minor (17%) types. Whereas, clones from the second and the third inocula as well as all post inoculation acute phase sera from both chimpanzees were mostly identical to the major type. Minor types of clone as same as in the first inocula were not detected in the second and the third inocula as well as all acute phase sera from both chimpanzees. In both chimpanzees, titers of antibody against the non-structure region were elevated post-2nd inoculation and were continuous, and those against the core region were elevated post-2nd and 3rd inoculations. On the other hand, titers of anti-HVR1 antibody showed a low titer in pre-and post-inoculation sera from both chimpanzees. The results showed that clones of the same strain of HCV with identical amino acid sequence could twice reinfect the same chimpanzee. The failure in developing an adequate anti-HVR1 antibody response in the chimpanzees with repeatedly reinfection even with the same strain of HCV indicated the complexity of HCV infection immunity.

为了研究相同基因的丙型肝炎病毒(HCV)是否可以两次再感染同一只黑猩猩，我们在黑猩猩模型中分析了I-IC V高变区1(HVR1)的氨基酸序列和免疫应答。用来自丙型肝炎病毒F株的含丙型肝炎病毒的血清接种63号和65号黑猩猩，共接种3次。在每次接种后，两只黑猩猩都出现了急性丙型肝炎合并病毒血症，然后随着丙型肝炎病毒RNA的消失而恢复。随后接种之间的间隔至少是在初次接种相关的丙型肝炎病毒RNA消失后一年。用黑猩猩各接种物和各接种后的急性期血清进行克隆、序列测定和氨基酸分析。检测抗丙型肝炎病毒非结构区、核心区和HVR1区的抗体效价。第一次接种的无性系可分为主要类型(83%)和次要类型(17%)。而第二次和第三次接种的克隆以及接种后两只黑猩猩的所有急性期血清与主要类型的克隆基本相同。在第二次和第三次接种以及两只黑猩猩的所有急性期血清中均未检测到与第一次接种相同的次要克隆类型。在两种黑猩猩中，针对非结构区的抗体效价在第2次免疫后升高，并持续存在，针对核心区的抗体效价在第2次和第3次免疫后升高。另一方面，两只黑猩猩在接种前和接种后的血清中，抗HVR1抗体的滴度都很低。结果表明，具有相同氨基酸序列的同一株丙型肝炎病毒克隆可以二次感染同一只黑猩猩。在反复再感染的黑猩猩中，即使用相同的丙型肝炎病毒株，也不能产生足够的抗HVR1抗体反应，这表明了丙型肝炎病毒感染免疫的复杂性。