Extensive analysis on HIV-1 core disassembly including the timing or triggering of uncoating
| Project/Area Number |
26460550
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Takeuchi Hiroaki 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (20451867)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | HIV-1 / HIV-1コア崩壊制御メカニズム / 宿主因子 / リン酸化 / uncoating / capsid |
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| Outline of Final Research Achievements |
Phosphorylation of the HIV-1 capsid has long been known to regulate viral uncoating and cDNA synthesis processes, but the cellular kinases responsible for this have remained unidentified. Here, we report that a host cell kinase MELK dictates optimal capsid disassembly through phosphorylation of Ser-149 in the multimerized HIV-1 core, which leads to efficient viral cDNA synthesis in target cells. The phosphorylation-mimetic capsid mutation of Ser-149 caused aberrant capsid disassembly and too-early completion of reverse transcription, and impeded nuclear entry of HIV-1 cDNA, suggesting the importance of well-ordered capsid disassembly in the early stages of viral replication. This discovery will facilitate understanding of the functional link among virus uncoating, reverse transcription and nuclear entry, and is expected to contribute to developing a novel strategy for AIDS therapy.
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Report
(4 results)
Research Products
(10 results)
