Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex.
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.
Yu
Xianghui
X
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Yu
Yunkai
Y
Liu
Bindong
B
Luo
Kun
K
Kong
Wei
W
Mao
Panyong
P
Yu
Xiao-Fang
XF
D000071480:APOBEC-3G Deaminase; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D003564:Cytidine Deaminase; D000075065:Elongin; D016346:Gene Products, vif / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009154:Mutation; D009700:Nucleoside Deaminases; D011506:Proteins / Q000378:metabolism*; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism*; D014779:Virus Replication; D054320:vif Gene Products, Human Immunodeficiency Virus
D002352:Carrier Proteins; D044842:Cullin Proteins; D000075065:Elongin; D016346:Gene Products, vif; D011506:Proteins; C479529:RBX1 protein, human; D012097:Repressor Proteins; D014157:Transcription Factors; D025801:Ubiquitin; D054320:vif Gene Products, Human Immunodeficiency Virus; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase