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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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2013: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2012: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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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 / AID / クラススイッチ / 感染抵抗性 / 遺伝子多型 / 標的細胞 / 持続感染 / 胚中心 / Bリンパ球 / TLR7 |
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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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Report
(4 results)
Research Products
(28 results)
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[Journal Article] Infection of adult thymus with murine retrovirus induces virus-specific central tolerance that prevents functional memory CD8+ T cell differentiation2014
Author(s)
Takamura S, Kajiwara E, Tsuji-Kawahara S, Masumoto T, Fujisawa M, Kato M, Chikaishi T, Kawasaki Y, Kinoshita S, Itoi M, Sakaguchi N, Miyazawa M
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Journal Title
DOI
Related Report
Peer Reviewed
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[Presentation] T細胞の交差反応性とHIV逃避変異の解析2013
Author(s)
本園千尋, J. J. Miles, Z. Hasan, 潟永博之, S. C. Meribe, D. A. Price, 岡慎一, 宮澤正顯, A. K. Sewell, 上野貴将
Organizer
白馬シンポジウム
Place of Presentation
名古屋
Related Report
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[Presentation] CD69 controls a balance between SIP- and CXCL16-induced chemotaxes during the process of memory CD8_+ T cell recruitment to the lung airways.2012
Author(s)
Takamura, S., J. E. Kohlmeier, H. Yagi, T. Nakayama, M. Tomura, K. Matsushima, D. L. Woodland, and M. Miyazawa
Organizer
Keystone Symposium on Viral Immunity and Host Gene Influence
Place of Presentation
Keystone, Colorado, U.S.A.
Related Report
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