HIV type 1 viral infectivity factor and the RUNX transcription factors interact with core binding factor β on genetically distinct surfaces

Judd F. Hultquist, Rebecca M. McDougle, Brett D. Anderson, Reuben S. Harris*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Human immunodeficiency virus type 1 (HIV-1) requires the cellular transcription factor core binding factor subunit β (CBFβ) to stabilize its viral infectivity factor (Vif) protein and neutralize the APOBEC3 restriction factors. CBFβ normally heterodimerizes with the RUNX family of transcription factors, enhancing their stability and DNA-binding affinity. To test the hypothesis that Vif may act as a RUNX mimic to bind CBFβ, we generated a series of CBFβ mutants at the RUNX/CBFβ interface and tested their ability to stabilize Vif and impact transcription at a RUNX-dependent promoter. While several CBFβ amino acid substitutions disrupted promoter activity, none of these impacted the ability of CBFβ to stabilize Vif or enhance degradation of APOBEC3G. A mutagenesis screen of CBFβ surface residues identified a single amino acid change, F68D, that disrupted Vif binding and its ability to degrade APOBEC3G. This mutant still bound RUNX and stimulated RUNX-dependent transcription. These separation-of-function mutants demonstrate that HIV-1 Vif and the RUNX transcription factors interact with cellular CBFβ on genetically distinct surfaces.

Original languageEnglish (US)
Pages (from-to)1543-1551
Number of pages9
JournalAIDS research and human retroviruses
Volume28
Issue number12
DOIs
StatePublished - Dec 1 2012

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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