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Article
APOBEC3G Genetic Variants and Their Influence on the Progression to AIDS
Journal of Virology
  • Ping An, National Cancer Institute at Frederick
  • Gabriela Bleiber, University of Lausanne - Switzerland
  • Priya Duggal, National Genome Research Institute
  • George Nelson, National Cancer Institute at Frederick
  • Margaret May, University of Bristol
  • Bastien Mangeat, University of Geneva - Switzerland
  • Irene Alobwede, University Hospital of Geneva - Switzerland
  • Didier Trono, University of Geneva - Switzerland
  • David Vlahov, Johns Hopkins Bloomberg School of Public Health
  • Sharyne Donfield, Rho, Inc.
  • James J. Goedert, National Cancer Institute at Bethesda
  • John Phair, Northwestern University Medical School
  • Susan Buchbinder, San Francisco Department of Public Health
  • Stephen J. O'Brien, National Cancer Institute at Frederick
  • Amalio Telenti, University of Lausanne - Switzerland
  • Cheryl Winkler, National Cancer Institute at Frederick
Document Type
Article
Publication Date
10-1-2004
Abstract

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.

Comments

© 2004, American Society for Microbiology

Additional Comments
NCI/NIH contract #: NO1-CO-124000; NIH grant: DA04334
ORCID ID
0000-0001-7353-8301
ResearcherID
N-1726-2015
Citation Information
Ping An, Gabriela Bleiber, Priya Duggal, George Nelson, et al.. "APOBEC3G Genetic Variants and Their Influence on the Progression to AIDS" Journal of Virology Vol. 78 Iss. 20 (2004) p. 11070 - 11076 ISSN: 0022-538X
Available at: http://works.bepress.com/stephen-obrien/50/