APOBEC3G mediated resistance to HIV-1 infection Authored: Matthews, L, 2006-06-07 20:09:24 Edited: Matthews, L, 2007-01-30 11:27:41 Pubmed12167863 Pubmed15098018 Pubmed15152192 Pubmed16414984 Reactome Database ID Release 43180689 Reactome, http://www.reactome.org ReactomeREACT_9406 Representatives of the apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3) family provide innate resistance to exogeneous and endogenous retroviruses (see Cullen 2006 for a recent review). Humans and other primates encode a cluster of seven different cytidine deaminases with APOBEC3G, APOBEC3F and APOBEC3B having some anti HIV-1 activity. Our understanding is most complete for APOBEC3G which has been described first and the reactions described herein will focus on this representative enzyme.<br><br>APOBEC3G is a cytoplasmic protein which strongly restricts replication of Vif deficient HIV-1 (Sheehy 2002). It is expressed in cell populations that are susceptible to HIV infection (e.g., T-lymphocytes and macrophages). In the producer cell, APOBEC3G is incorporated into budding HIV-1 particles through an interaction with HIV-1 gag nucleocapsid (NC) protein in a RNA-dependent fashion. <br><br>Within the newly infected cell (= target cell), virus-associated APOBEC3G regulates the infectivity of HIV-1 by deaminating cytidine to uracil in the minus-strand viral DNA intermediate during reverse transcription. Deamination results in the induction of G-to-A hypermutations in the plus-strand viral DNA which subsequently can either be integrated as a non-functional provirus or degraded before integration. Reviewed: Mulder, L, 2007-01-30 22:57:00 Reviewed: Simon, V, 2007-01-30 23:07:12 PathwayStep3632 PathwayStep3631 PathwayStep3633 Association of APOBEC3G with Gag Association of APOBEC3G with single-stranded region of forming HIV-1 minus strand Deamination of C residues during synthesis of HIV-1 reverse transcript minus-strand