Extensive analysis on HIV-1 core disassembly including the timing or triggering of uncoating

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460550
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: Tokyo Medical and Dental University
• 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)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: HIV-1

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.

Free Research Field

ウイルス学