| Project/Area Number |
14370103
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | The University of Tokushima |
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Principal Investigator |
ADACHI Akio The University of Tokushima, Graduate School Institute of Health Biosciences, Professor, 大学院・ヘルスバイオサイエンス研究部, 教授 (90127043)
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| Co-Investigator(Kenkyū-buntansha) |
KOYAMA Hajime Wakayama Medical University, Professor, 教授 (80109074)
UCHIYAMA Tsuneo The University of Tokushima, Graduate School Institute of Health Biosciences, Associate Professor, 大学院・ヘルスバイオサイエンス研究部, 助教授 (90151901)
FUJITA Mikako The University of Tokushima, Graduate School Institute of Health Biosciences, Assistant Professor, 大学院・ヘルスバイオサイエンス研究部, 助手 (00322256)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2004: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2002: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | HIV-1 / HIV-2 / Vif / Nef / Vpr / Vpx / proteasome-degradation / SIV / ルシフェラーゼ / Vpu |
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| Research Abstract |
In this study, we have done functional domain analyses on Vif and Nef of HIV-1, and also on Vpx and Vpr of HIV-2. Results obtained can be summarized as follows. (1) HIV-1 Vif. By comparing the activities of Vif from long term nonprogressors and progressors for AIDS, we found that Vif could influence HIV-1 infectivity and disease progression in infected individuals. We have constructed a series of HIV-1 Vif mutants in vitro, and have characterized them biologically and biochemically. During the course of this mutational analysis, we noticed that HIV-1 Vif is extremely and uniquely sensitive to proteasome-degradation among HIV accessory proteins. We identified the lysine residues responsible for this degradation, and showed that it is critically important for the optimal infectivity of HIV-1. (2) HIV-1 Nef. By using a point mutant of Nef which is defective only for MHC-I down-regulation, we have demonstrated that HIV-1 Nef suppresses the cytokine production by CTL cells only partially, while completely their cytocydial activity. (3) HIV-2 Vpx and Vpr. In additoin to Vpr, which is also encoded by the genome of HIV, HIV-2 carries Vpx in its genome. By homology modeling, it has been clearly and strongly suggested that HIV-1 Vpr, HIV-2 Vpx and HIV-2 Vpr are structurally very similar, having three or four major helices. In our functional mutational study, HIV-2 Vpx and Vpr were found to have more functions than HIV-1 Vpr such as enhancing reverse transcription of viral genome and augmenting virion release.
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