A comprehensive protein interaction analysis for developing new therapeutic targets in HIV infection using cell-free protein synthesis technology

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390115
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: Yokohama City University
• Principal Investigator: RYO Akihide 横浜市立大学, 医学(系)研究科(研究院), 教授 (20363814)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: ウイルス / タンパク質 / プロテオーム / 酵素 / バイオテクノロジー / HIV / 宿主因子

Outline of Final Research Achievements

In this study, we took advantage of the comprehensive protein interaction analysis using cell-free protein synthesis technology. We established an assay system for monitoring the functional interaction between HIV accessory proteins and intrinsic anti-virus host factors. Using this system, we found that apoptosis signal-regulating kinase 1 (ASK1) interferes with the counteraction of Vif and revitalizes the A3G-mediated viral restriction. ASK1 binds the BC-box of Vif, thereby disrupting the assembly of the Vif-ubiquitin ligase complex. Consequently, ASK1 stabilizes A3G and promotes its incorporation into viral particles, ultimately reducing viral infectivity. Furthermore, treatment with the antiretroviral AZT (zidovudine) induces ASK1 expression and restores the antiviral activity of A3G in HIV-1-infected cells. This study thus demonstrates a distinct function of ASK1 in restoring the host antiviral system that can be enhanced by AZT treatment.

Free Research Field

ウイルス学