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


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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