2014 Fiscal Year Final Research Report
Mechanisms of regulation of host immune responses by retrovirus-restricting enzyme APOBEC3
| Project/Area Number |
24390116
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Kinki University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KAWAHARA Sachiyo 近畿大学, 医学部, 講師 (60297629)
HAKATA Yoshiyuki 近畿大学, 医学部, 助教 (30344500)
TAKAMURA Shiki 近畿大学, 医学部, 助教 (90528564)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | レトロウイルス / 中和抗体 / APOBEC3 / 体細胞高頻度突然変異 / Tリンパ球 / 胸腺 |
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| Outline of Final Research Achievements |
APOBEC3 is a DNA mutator that restricts retrovirus replication, and its allelic differences have been associated with kinetics of the production of virus-neutralizing antibodies. We wished to elucidate how APOBEC3 affects antibody production.
CD8+ T cells were dispensable while CD4+ T cells were crucial for the elimination of virus-infected erythroid cells. In the absence of B-lymphocytes, infected erythroid cells were eliminated but retrovirus replication persisted in myeloid cells. Friend retrovirus also infected the thymus, and thymic expression of the viral antigens lead to negative selection of virus-specif T cells. Further, mice lacking activation-induced cytidine deaminase nevertheless produced neutralizing antibodies, and non-mutated IgM conferred resistance to infection in the presence of virus antigen-primed CD4+ T cells. Thus, APOBEC3 seems to interfere with virus-induced derangement of CD4+ T-cell functions that are crucial for the production of neutralizing antibodies.
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| Free Research Field |
ウイルス学
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