Molecular basis underlying different antiviral functions in the APOBEC3 family

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04740
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: National Hospital Organization Nagoya Medical Center
• Principal Investigator: Iwatani Yasumasa 独立行政法人国立病院機構(名古屋医療センター臨床研究センター), その他部局等, 部長 (90303403)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: レトロウイルス / 宿主因子 / APOBEC3 / 感染制御 / 核酸結合 / 構造解析 / 生化学 / HIV

Outline of Final Research Achievements

Cellular enzymes of the APOBEC3 family (7 members encoded in human) exhibit potent antiviral activity against retroviruses including HIV. However, HIV expresses viral factor, Vif protein, in its infected cells and abrogates the APOBEC3-mediated defense system. Structural determinations of APOBEC3 family proteins are required to understand their antiviral functions and Vif-mediated antagonisms. In this study, we determined high-resolution crystal structures of APOBEC3 family proteins (2 of them) and clarified their structural/biochemical features underlying their molecular mechanisms. Especially, our determination of APOBEC3H crystal structure and unexpected findings of its biochemical properties provide important insights into the APOBEC3-mediated antiviral mechanisms as well as cancer and genetic mutations.

Free Research Field

ウイルス学