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Vif hijacks CBF-β to degrade APOBEC3G and promote HIV-1 infection.

Nature | Dec 21, 2011

Restriction factors, such as the retroviral complementary DNA deaminase APOBEC3G, are cellular proteins that dominantly block virus replication. The AIDS virus, human immunodeficiency virus type 1 (HIV-1), produces the accessory factor Vif, which counteracts the host's antiviral defence by hijacking a ubiquitin ligase complex, containing CUL5, ELOC, ELOB and a RING-box protein, and targeting APOBEC3G for degradation. Here we reveal, using an affinity tag/purification mass spectrometry approach, that Vif additionally recruits the transcription cofactor CBF-β to this ubiquitin ligase complex. CBF-β, which normally functions in concert with RUNX DNA binding proteins, allows the reconstitution of a recombinant six-protein assembly that elicits specific polyubiquitination activity with APOBEC3G, but not the related deaminase APOBEC3A. Using RNA knockdown and genetic complementation studies, we also demonstrate that CBF-β is required for Vif-mediated degradation of APOBEC3G and therefore for preserving HIV-1 infectivity. Finally, simian immunodeficiency virus (SIV) Vif also binds to and requires CBF-β to degrade rhesus macaque APOBEC3G, indicating functional conservation. Methods of disrupting the CBF-β-Vif interaction might enable HIV-1 restriction and provide a supplement to current antiviral therapies that primarily target viral proteins.

Pubmed ID: 22190037 RIS Download

Mesh terms: APOBEC-3G Deaminase | Affinity Labels | Animals | Core Binding Factor beta Subunit | Cullin Proteins | Cytidine Deaminase | Gene Knockdown Techniques | Gene Products, vif | Genetic Complementation Test | HEK293 Cells | HIV Infections | HIV-1 | Host-Pathogen Interactions | Humans | Jurkat Cells | Macaca mulatta | Mass Spectrometry | Models, Biological | Protein Binding | Proteolysis | Simian Immunodeficiency Virus | Ubiquitin-Protein Ligases | Ubiquitination | Virus Replication | vif Gene Products, Human Immunodeficiency Virus

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Associated grants

  • Agency: NIAID NIH HHS, Id: T32 AI083196
  • Agency: NIGMS NIH HHS, Id: P41 GM103481
  • Agency: NCRR NIH HHS, Id: P41RR001614
  • Agency: NIGMS NIH HHS, Id: T32 GM008284
  • Agency: NIGMS NIH HHS, Id: P50GM081879
  • Agency: NIGMS NIH HHS, Id: P50 GM081879
  • Agency: NCRR NIH HHS, Id: U54 RR022220
  • Agency: NIGMS NIH HHS, Id: P50 GM082250-05
  • Agency: NIGMS NIH HHS, Id: P50 GM082250
  • Agency: NIGMS NIH HHS, Id: P01 GM091743
  • Agency: NIAID NIH HHS, Id: R01 AI064046
  • Agency: NCRR NIH HHS, Id: P41 RR001614
  • Agency: NIAID NIH HHS, Id: P01 AI090935

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