Title

APOBEC3G Genetic Variants and Their Influence on the Progression to AIDS

Authors

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 FrederickFollow
Amalio Telenti, University of Lausanne - Switzerland
Cheryl Winkler, National Cancer Institute at Frederick

Document Type

Article

Publication Date

10-2004

Publication Title

Journal of Virology

ISSN

0022-538X

Volume

78

Issue/No.

20

First Page

11070

Last Page

11076

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

NSUWorks Citation

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. https://nsuworks.nova.edu/cnso_bio_facarticles/209

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015