Induction of APOBEC3G Ubiquitination and Degradation by an HIV-1 Vif-Cul5-SCF Complex
Xianghui Yu,1,2*
Yunkai Yu,1*
Bindong Liu,1*
Kun Luo,1
Wei Kong,2
Panyong Mao,1
Xiao-Fang Yu1,3
Human immunodeficiency virus–1 (HIV-1) Vif is essential for viral evasion of host antiviral factor CEM15/APOBEC3G. We report that Vif interacts with cellular proteins Cul5, elongins B and C, and Rbx1 to form an Skp1-cullin-F-box (SCF)–like complex. The ability of Vif to suppress antiviral activity of APOBEC3G was specifically dependent on Cul5-SCF function, allowing Vif to interact with APOBEC3G and induce its ubiquitination and degradation. A Vif mutant that interacted with APOBEC3G but not with Cul5-SCF was functionally inactive. The Cul5-SCF was also required for Vif function in distantly related simian immunodeficiency virus mac. These results indicate that the conserved Cul5-SCF pathway used by Vif is a potential target for antiviral development.
1 Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
2 Jilin University, Jilin, People's Republic of China.
3 Zhejiang University, Zhejiang, People's Republic of China.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: xfyu{at}jhsph.edu
