Journal of Virology
The cytosine deaminase APOBEC3G, in the absence of the human immunodeficiency virus type 1 (HIV-1) accessory gene HIV-1 viral infectivity factor (vif), inhibits viral replication by introducing G→A hypermutation in the newly synthesized HIV-1 DNA negative strand. We tested the hypothesis that genetic variants of APOBEC3G may modify HIV-1 transmission and disease progression. Single nucleotide polymorphisms were identified in the promoter region (three), introns (two), and exons (two). Genotypes were determined for 3,073 study participants enrolled in six HIV-AIDS prospective cohorts. One codon-changing variant, H186R in exon 4, was polymorphic in African Americans (AA) (f < 37%) and rare in European Americans (f < 3%) or Europeans (f = 5%). For AA, the variant allele 186R was strongly associated with decline in CD4 T cells (CD4 slope on square root scale: -1.86, P = 0.009), The 186R allele was also associated with accelerated progression to AIDS-defining conditions in AA. The in vitro antiviral activity of the 186R enzyme was not inferior to that of the common H186 variant. These studies suggest that there may be a modifying role of variants of APOBEC3G on HIV-1 disease progression that warrants further investigation.
An, Ping; Gabriela Bleiber; Priya Duggal; George Nelson; Margaret May; Bastien Mangeat; Irene Alobwede; Didier Trono; David Vlahov; Sharyne Donfield; James J. Goedert; John Phair; Susan Buchbinder; Stephen J. O'Brien; Amalio Telenti; and Cheryl Winkler. 2004. "APOBEC3G Genetic Variants and Their Influence on the Progression to AIDS." Journal of Virology 78, (20): 11070-11076. http://nsuworks.nova.edu/cnso_bio_facarticles/209