We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Vif hijacks CBF-? to degrade APOBEC3G and promote HIV-1 infection.
- Authors
Jäger, Stefanie; Kim, Dong Young; Hultquist, Judd F.; Shindo, Keisuke; LaRue, Rebecca S.; Kwon, Eunju; Li, Ming; Anderson, Brett D.; Yen, Linda; Stanley, David; Mahon, Cathal; Kane, Joshua; Franks-Skiba, Kathy; Cimermancic, Peter; Burlingame, Alma; Sali, Andrej; Craik, Charles S.; Harris, Reuben S.; Gross, John D.; Krogan, Nevan J.
- Abstract
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-? to this ubiquitin ligase complex. CBF-?, 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-? 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-? to degrade rhesus macaque APOBEC3G, indicating functional conservation. Methods of disrupting the CBF-?-Vif interaction might enable HIV-1 restriction and provide a supplement to current antiviral therapies that primarily target viral proteins.
- Publication
Nature, 2012, Vol 481, Issue 7381, p371
- ISSN
0028-0836
- Publication type
Academic Journal
- DOI
10.1038/nature10693