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

Article

关键词: UBIQUITIN-LIGASE COMPLEX;    SOCS-BOX;    RESTRICTION FACTORS;    ANTIVIRAL ACTIVITY;    PROTEIN;    SPECIFICITY;    PROTEASOME;    MECHANISM;    TARGETS;    TISSUES;   

DOI  :  10.1038/nature10693

来源: SCIE

【 摘 要 】

Restriction factors, such as the retroviral complementary DNA deaminase APOBEC3G, are cellular proteins that dominantly block virus replication(1-3). The AIDS virus, human immuno deficiency 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(4-10). Here we reveal, using an affinity tag/purification mass spectrometry approach, that Vif additionally recruits the transcription cofactor CBF-beta to this ubiquitin ligase complex. CBF-beta, 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-beta 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-beta to degrade rhesus macaque APOBEC3G, indicating functional conservation. Methods of disrupting the CBF-beta-Vif interaction might enable HIV-1 restriction and provide a supplement to current antiviral therapies that primarily target viral proteins.

【 授权许可】

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