| Project/Area Number |
11670302
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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 |
Virology
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| Research Institution | SAITAMA MEDICAL SCHOOL |
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Principal Investigator |
AKATSUKA Toshitaka Professor, Faculty of Medicine, Saitama Medical School, 医学部, 教授 (30159321)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUURA Yoshiharu Chief, Laboratory of Virology II, National Institute of Infectious Diseases, ウイルスII部, 室長 (50157252)
KANKI Taizanburo Lecturer, Faculty of Medicine, Saitama Medical School, 医学部, 講師 (10124918)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Chimpanzee / Hepatitis C / Hepatitis C virus / Neutralizing antibodies / B-cells / EB virus / ELISA / Peptides / ELISA |
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| Research Abstract |
C.Rice and S.Feintone have succeeded in infection of monoclonal hepatitis C virus (HCV) by inoculating transcribed RNA from full-length cDNA into the liver of two chimpanzees. We transformed B-cells in peripheral blood lymphocytes from those chimps, and investigated the appearance of B-cell clones producing HCV-specific IgG.IgG antibody titers in serum samples were also investigated. Both chimps had IgG antibody against HCV core antigen on week 20 after inoculation when ALT elevation was noted. However, anti-E1 or anti-E2 IgG could be detected only in chimp 1365 on week 45, which continued to increase in titer for 10 weeks. In EBV-transformation experiments, B-cells producing IgG against C, E1 or E2 were found at the same frequency on week 35 which was similar to that on week 54. These data suggested that differentiation of B-cell that have potential to produce anti-E1 and anti-E2 are suppressed by some mechanisms at their final stage. S.Feinstone has found that a mutant HCV with singl
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e amino acid substitution in E2 appeared and dominated at almost the same time as the appearance of anti-E2 IgG antibody in sera in chimp 1536. Because the rapid increase of anti-E2 titer took place at the same time, we suspected that the mutation of E2 induced helper T-cell response to help class switch of anti-E2 producing B-cells. Therefore, two peptides with the original and mutated sequence of E2 were synthesized and tested in proliferation assay of PBL from both chimps. However, ther were no positive response, and our hypothesis could not have a supportive data. Then, IgM as well as IgG response was measured, and unexpectedly, it was found to appear very late in the convalescent phase in parallel to increase of IgG antibody titer. This anusualfinding suggests that the immune system of infected chimps had the second stimulation at this time probably because the mutated virus behaved differently from the original one. We found that B-cell in the convalescent phase express HCV structural proteins. It might be related to this change of the sequence and behavior of the virus, and need further pursuit. Less
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