Open AccessConserved and non‐conserved features of HIV‐1 and SIVagm Vif mediated suppression of APOBEC3 cytidine deaminases
Author(s) -
Zhang Wenyan,
Huang Michael,
Wang Tao,
Tan Lindi,
Tian Chunjuan,
Yu Xianghui,
Kong Wei,
Yu XiaoFang
Publication year - 2008
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2008.01157.x
Subject(s) - biology , cytidine deaminase , apobec3g , ubiquitin ligase , simian immunodeficiency virus , ubiquitin , cytidine , genetics , mutation , virology , dna ligase , microbiology and biotechnology , virus , biochemistry , enzyme , gene
Summary Human cytidine deaminase APOBEC3C (A3C) acts as a potent inhibitor of SIVagm and can be regulated by both HIV‐1 and SIVagm Vif. The mechanism by which Vif suppresses A3C is unknown. In the present study, we demonstrate that both HIV‐1 and SIVagm Vif can act in a proteasome‐dependent manner to overcome A3C. SIVagm Vif requires the Cullin5‐ElonginB‐ElonginC E3 ubiquitin ligase for the degradation of A3C as well as the suppression of its antiviral activity. Mutation of a residue critical for the species‐specific recognition of human or monkey A3G by HIV‐1 Vif or SIVagm Vif in A3C had little effect on HIV‐1 or SIVagm Vif‐mediated degradation of A3C. Although the amino‐terminal region of A3G was not important for Vif‐mediated degradation, the corresponding region in A3C was critical. A3C mutants that were competent for Vif binding but resistant to Vif‐mediated degradation were identified. These data suggest that primate lentiviral Vif molecules have evolved to recognize multiple host APOBEC3 proteins through distinct mechanisms. However, Cul5‐E3 ubiquitin ligase appears to be a common pathway hijacked by HIV‐1 and SIV Vif to defeat APOBEC3 proteins. Furthermore, Vif and APOBEC3 binding is not sufficient for target protein degradation indicating an important but uncharacterized Vif function.