Molecular mechanism of viral suppression by APOBEC3

• Project/Area Number: 18K07142
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49060:Virology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Ito Nobutoshi 東京医科歯科大学, 難治疾患研究所, 教授 (40361703)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 蛋白質間相互作用 / 抗ウイルス蛋白質 / レトロウイルス

Outline of Final Research Achievements

APOBEC3 is one of the molecular mechanisms against retroviruses and uses its cytidine-deaminase activity to suppress the virus. Recently mouse APOBEC3 (mA3) was reported to suppress viruses in a deaminase-independent way, by inhibiting the process of gag-pol precursor. In this study, we prepared the C-terminal Z domain of mA3 and measured its interaction with viral protease. No direct interactions were observed between them and, together with the fact that the N-terminal Z domain of mA3 interacts weakly with the protease, it is strongly the full-length mA3 is required for sufficient interaction with the protease.

Academic Significance and Societal Importance of the Research Achievements

レトロウイルスには免疫不全症候群を引き起こすHIVなど様々な病原体が含まれており、人類にとって大きな健康リスクとなっている。これまで知られていなかったウイルス抑制機構の理解は、関連する疾患の新しい治療薬の開発につながる可能性があり、本研究はその研究の基盤となることが期待される。