Dispersed and conserved hydrophobic residues of HIV-1 vif are essential for CBFβ recruitment and A3G suppression

Xiaohong Zhou, Xue Han, Ke Zhao, Juan Du, Sean L. Evans, Hong Wang, Peng Li, Wenwen Zheng, Yajuan Rui, Jian Kang, Xiao Fang Yu

Research output: Contribution to journalArticlepeer-review

Abstract

CBFβ was recently found to be a key regulator of the ability of human immunodeficiency virus type 1 (HIV-1) Vif to overcome host antiviral APOBEC3 proteins. However, the detailed molecular requirements for the Vif-CBFβ interaction are still not clear. Here, we mapped the minimum Vif domain required for CBFβ binding. In terms of CBFβ binding, the Vif N terminus was very sensitive to deletions. We determined that the Vif fragment from residues 5 to 126 was sufficient to form a stable complex with CBFβ in vitro. We also observed that ionic interactions were not the main contributor to the interaction between Vif and CBFβ. Instead, hydrophobic interactions were important for maintaining the Vif-CBFβ complex, since it could be disrupted by nonionic detergent. Site-directed mutagenesis of conserved hydrophobic amino acids revealed novel residues in Vif that were important for CBFβ binding and APOBEC3 inactivation. At least part of the well-characterized HCCH domain (residues 108 to 139) was required to form a stable Vif-CBFβ complex. Thus, the HCCH motif may have a dual role in binding both Cul5 and CBFβ. Considering the importance of Vif in HIV-1 infection, this unique Vif-CBFβ interaction represents an attractive pharmacological intervention target against HIV-1.

Original languageEnglish (US)
Pages (from-to)2555-2563
Number of pages9
JournalJournal of virology
Volume88
Issue number5
DOIs
StatePublished - Mar 2014
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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