Role of A3G acetylation and Vif/HDAC3 complex in HIV-1 infection

Research Project

Project/Area Number	16K08809
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Virology
Research Institution	Kyoto University
Principal Investigator	Shirakawa Kotaro 京都大学, 医学研究科, 助教 (80728270)
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000) Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords	HIV-1 / Vif / ヒストン脱アセチル化酵素 / DNAシトシン脱アミノ化酵素APOBEC3G / 潜伏感染 / HIV感染症 / HIV-1 Vif / APOBEC3G / アセチル化 / HDAC3 / シチジン脱アミノ化酵素
Outline of Final Research Achievements	1) We identified that five lysine residues of APOBEC3G are aceylated and deacetylated by HDAC3. Its non-acetylated Arginine mutant is less sensitive to Vif mediated degradation. 2) Latently HIV-1 infected T-cells are sorted and its gene expression profile is compared to virus producing cells and non-infected cells. We identified 33 genes specifically down-regulated in latently infected cells and two genes specifically up-regulated genes compared to non-infected cells.
Academic Significance and Societal Importance of the Research Achievements	ウイルスが細胞のメカニズムをハイジャックして利用するその一端を発見した。HIV-1感染症を克服するためには、潜伏感染するために必要なメカニズムを明らかにする必要があり、本研究で潜伏感染細胞を分離しその遺伝子発現変化を解析できたことは新たなステップになると考えられる。