Defining HIV-1 Vif residues that interact with CBFβ by site-directed mutagenesis

Yusuke Matsui, Keisuke Shindo, Kayoko Nagata, Katsuhiro Io, Kohei Tada, Fumie Iwai, Masayuki Kobayashi, Norimitsu Kadowaki, Reuben S. Harris, Akifumi Takaori-Kondo

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Vif is essential for HIV-1 replication in T cells and macrophages. Vif recruits a host ubiquitin ligase complex to promote proteasomal degradation of the APOBEC3 restriction factors by poly-ubiquitination. The cellular transcription cofactor CBFβ is required for Vif function by stabilizing the Vif protein and promoting recruitment of a cellular Cullin5-RING ubiquitin ligase complex. Interaction between Vif and CBFβ is a promising therapeutic target, but little is known about the interfacial residues. We now demonstrate that Vif conserved residues E88/W89 are crucial for CBFβ binding. Substitution of E88/W89 to alanines impaired binding to CBFβ, degradation of APOBEC3, and virus infectivity in the presence of APOBEC3 in single-cycle infection. In spreading infection, NL4-3 with Vif E88A/W89A mutation replicated comparably to wild-type virus in permissive CEM-SS cells, but not in multiple APOBEC3 expressing non-permissive CEM cells. These results support a model in which HIV-1 Vif residues E88/W89 may participate in binding CBFβ.

Original languageEnglish (US)
Pages (from-to)82-87
Number of pages6
StatePublished - Jan 20 2014

Bibliographical note

Funding Information:
This study was partly supported by Grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology and from the Ministry of Health, Labor and Welfare in Japan . Work in the Harris lab was supported in part by grants from the National Institutes of Health ( R01 AI064046 and P01 GM091743).


  • CBFβ
  • HIV-1
  • Host factors
  • Interaction
  • Vif


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