A single amino acid difference in human APOBEC3H variants determines HIV-1 Vif sensitivity

Anjie Zhen, Tao Wang, Ke Zhao, Yong Xiong, Xiao Fang Yu

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


Several variants of APOBEC3H (A3H) have been identified in different human populations. Certain variants of this protein are particularly potent inhibitors of retrotransposons and retroviruses, including HIV-1. However, it is not clear whether HIV-1 Vif can recognize and suppress the antiviral activity of A3H variants, as it does with other APOBEC3 proteins. We now report that A3H-Haplotype II (HapII), a potent inhibitor of HIV-1 in the absence of Vif, can indeed be degraded by HIV-1 Vif. Vif-induced degradation of A3H-HapII was blocked by the proteasome inhibitor MG132 and a Cullin5 (Cul5) dominant negative mutant. In addition, Vif mutants that were incapable of assembly with the host E3 ligase complex factors Cul5, ElonginB, and ElonginC were also defective for A3H-HapII suppression. Although we found that Vif hijacks the same E3 ligase to degrade A3H-HapII as it does to inactivate APOBEC3G (A3G) and APOBEC3F (A3F), more Vif motifs were involved in A3H-HapII inactivation than in either A3G or A3F suppression. In contrast to A3H-HapII, A3H-Haplotype I (HapI), which differs in only three amino acids from A3H-HapII, was resistant to HIV-1 Vif-mediated degradation. We also found that residue 121 was critical for determining A3H sensitivity and binding to HIV-1 Vif.

Original languageEnglish (US)
Pages (from-to)1902-1911
Number of pages10
JournalJournal of virology
Issue number4
StatePublished - Feb 2010
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology


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