Your browser version may not work well with NCBI's Web applications. More information here...
1: J Biol Chem. 2008 Feb 1;283(5):2518-25. Epub 2007 Dec 5.
Related Articles, Links
Click here to read
Vpr.A3A chimera inhibits HIV replication.

Aguiar RS, Lovsin N, Tanuri A, Peterlin BM.

Department of Medicine, Microbiology, and Immunology, University of California at San Francisco, 533 Parnassus Avenue, San Francisco, CA 94143-0703, USA.

Several APOBEC3 proteins (A3F and A3G), that are cytidine deaminases restrict human immunodeficiency virus (HIV) replication in the absence of the viral infectivity factor (Vif) protein. However, Vif leads to their degradation and counteracts their effects. Another member, A3A, restricts some retrotransposons and another virus but not HIV. We reasoned that this failure was due to the lack of appropriate targeting. Thus, we fused A3A to another viral protein, Vpr, which binds p6 in Gag and is incorporated into viral cores. Indeed, the Vpr.A3A chimera but not A3A was found abundantly in the viral core. It also restricted potently the replication of HIV and simian immunodeficiency virus in the presence and absence of Vif. Because we identified a high frequency of G to A mutations in viral cDNAs, this antiviral activity was mediated by DNA editing. Interestingly, our fusion protein did not restrict murine leukemia virus, which does not incorporate Vpr. Thus, by targeting appropriately a potent single domain cytidine deaminase, we rendered HIV and simian immunodeficiency virus restriction resistant to Vif.

Publication Types:
PMID: 18057006 [PubMed - indexed for MEDLINE]