Vif-mediated degradation of APOBEC3G Authored: Matthews, L, 2006-05-15 23:53:25 Edited: Matthews, L, 2007-01-30 11:27:41 Pubmed12167863 Pubmed14527406 Pubmed14528300 Pubmed14564014 Pubmed15781449 Pubmed16354571 Reactome Database ID Release 43180585 Reactome, http://www.reactome.org ReactomeREACT_9453 Reviewed: Mulder, L, 2007-01-30 22:57:00 Reviewed: Simon, V, 2007-01-30 23:07:12 The HIV-1 accessory protein Vif (Viral infectivity factor) is required for the efficient infection of primary cell populations (e.g., lymphocytes and macrophages) and “non-permissive” cell lines. Vif neutralises the host DNA editing enzyme, APOBEC3G, in the producer cell. Indeed, in the absence of a functional Vif, APOBEC3G is selectively incorporated into the budding virions and in the next cycle of infection leads to the deamination of deoxycytidines (dC) within the minus-strand cDNA during reverse transcription (Sheehy et al 2003; Li et al., 2005 ; Stopak et al. 2003).<br>Deamination changes cytidine to uracil and thus results in G to A transitions and stop codons in the provirus. The aberrant cDNAs produced in the infected cell can either be integrated in form of non-functional proviruses or degraded. Vif counteracts the antiviral activity of APOBEC3G by associating directly with it and promoting its polyubiquitination and degradation by the 26S proteasome. <br>Vif binds APOBEC3G and recruits it into an E3 ubiquitin-enzyme complex composed by the cytoplasmic proteins Cullin5, Rbx, ElonginC and ElonginB (Yu et al., 2003) . Thus, in the presence of Vif, APOBEC3G incorporation into the virion is minimal.<br> PathwayStep3636 PathwayStep3635 PathwayStep3638 PathwayStep3637 Association of Vif with APOBEC3G Association of APOBEC3G:Vif with the Cul5-SCF complex Multi-ubiquitination of APOBEC3G Proteosome-mediated degradation of APOBEC3G