| Project/Area Number |
14570203
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Nihon University |
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Principal Investigator |
SUGITANI Masahiko Nihon University, School of Medicine, Associate Professor, 医学部, 助教授 (40187654)
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| Co-Investigator(Kenkyū-buntansha) |
SHEIKH Aleemuzzaman Nihon University, School of Medicine, Assistant, 医学部, 助手 (10277436)
MORIYAMA Mitsuhiko Nihon University, School of Medicine, Associate Professor, 医学部, 助教授 (50191060)
ABE Kenji National Institute of Infectious Diseases, Infectious Pathology, Senior Researcher, 感染病理部, 主任研究官 (60130415)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Hepatitis C virus (HCV) / Hypervariable region-1 / Chimpanzee / Reinfection experiment / HCV cloning / Anti-HCV antibody / hepatitis C virus / chimpanzee / HCV genotype |
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| Research Abstract |
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.
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