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

AIDS Res Hum Retroviruses. 2012 Dec;28(12):1543-51. doi: 10.1089/AID.2012.0142. Epub 2012 Aug 13.

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.

MeSH terms

  • APOBEC-3G Deaminase
  • Amino Acid Substitution
  • Core Binding Factor alpha Subunits / metabolism*
  • Core Binding Factor beta Subunit / genetics
  • Core Binding Factor beta Subunit / metabolism*
  • Cytidine Deaminase / metabolism*
  • HIV-1 / pathogenicity*
  • Host-Pathogen Interactions*
  • Humans
  • Mutagenesis, Site-Directed
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Protein Binding
  • Protein Interaction Mapping*
  • Proteolysis
  • vif Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • Core Binding Factor alpha Subunits
  • Core Binding Factor beta Subunit
  • Mutant Proteins
  • vif Gene Products, Human Immunodeficiency Virus
  • vif protein, Human immunodeficiency virus 1
  • APOBEC-3G Deaminase
  • APOBEC3G protein, human
  • Cytidine Deaminase