| 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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| 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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