Investigation of the roles of Vpr and regulatory T cells in the acute phase HIV-1 infection
| Project/Area Number |
23790500
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Virology
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| Research Institution | Kyoto University |
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Principal Investigator |
SATO Kei 京都大学, ウイルス研究所, 助教 (10593684)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | HIV-1 / Vpr / ヒト化マウス / 制御性T細胞 / 感染急性期 / HIV / エイズ / ウイルス / 感染病態 / ウイルス因子 |
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| Research Abstract |
Regulatory CD4+T cells (Tregs) are known for playing a pivotal role in the maintenance of immune homeostasis, and actively cycle in vivo. It is also known that human immunodeficiency virus type 1 (HIV-1) mainly targets CD4+T cells and induces immune activation as a hallmark of HIV-1 pathogenesis. Here, by using a humanized mouse model, we demonstrate that viral protein R (Vpr), a pleiotropic protein encoded by HIV-1, promotes viral expansion by exploiting Tregs during the acute phase of infection. Our findings show that Vpr predominantly causes G2 cell cycle arrest and apoptosis in Tregs, leading to their depletion in vivo. Moreover, we demonstrate that the Treg depletion caused by Vpr induces immune activation, which augments HIV-1 propagation in vivo. Taken together, this is the first report to directly demonstrate that Vpr plays a bifunctional role in HIV-1 replication in vivo by targeting Tregs and suggests that Vpr plays a crucial role in HIV-1 pathogenesis.
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Report
(3 results)
Research Products
(29 results)
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[Journal Article] Quantification system for the viral dynamics of a highly pathogenic simian/human immunodeficiency virus based on an in vitro experiment and a mathematical model.2012
Author(s)
Iwami, S., Holder, B. P., Beauchemin,C. A. A., Morita, S., Tada, T., Sato, K.,Igarashi, T., and Miura, T.
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Journal Title
Retrovirology
Volume: 9
Issue: 1
Pages: 18-18
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] A novel animal model of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in humanized mice2011
Author(s)
Sato K, Misawa N, Nie C, Satou Y, Iwakiri D, Matsuoka M, Takahashi R, Kuzushima K, Ito M, Takada K, Koyanagi Y
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Journal Title
Blood
Volume: 117
Issue: 21
Pages: 5663-5673
DOI
Related Report
Peer Reviewed
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