APOBEC3G genetic variants and their influence on the progression to AIDS.

نویسندگان

  • Ping An
  • 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
  • Cheryl A Winkler
چکیده

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.

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عنوان ژورنال:
  • Journal of virology

دوره 78 20  شماره 

صفحات  -

تاریخ انتشار 2004