This Article Full Text Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by An, P. Articles by Winkler, C. A. Search for Related Content PubMed PubMed Citation Articles by An, P. Articles by Winkler, C. A.

 Previous Article  |  Next Article 

Journal of Virology, October 2004, p. 11070-11076, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11070-11076.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

APOBEC3G Genetic Variants and Their Influence on the Progression to AIDS

Ping An,^1, Gabriela Bleiber,^2, Priya Duggal,³ George Nelson,¹ Margaret May,⁴ Bastien Mangeat,⁵ Irene Alobwede,⁶ Didier Trono,⁵ David Vlahov,⁷ Sharyne Donfield,⁸ James J. Goedert,⁹ John Phair,¹⁰ Susan Buchbinder,¹¹ Stephen J. O'Brien,¹² Amalio Telenti,² and Cheryl A. Winkler^1*

Basic Research Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center,¹ Laboratory of Genomic Diversity, National Cancer Institute, Frederick,¹² Inherited Disease Research Branch, National Human Genome Research Institute,³ Johns Hopkins University Bloomberg School of Public Health, Baltimore,⁷ Viral Epidemiology Branch, National Cancer Institute, Bethesda, Maryland,⁹ Rho Inc., Chapel Hill, North Carolina,⁸ Fineberg School of Medicine, Northwestern University, Comprehensive AIDS Center, Chicago, Illinois,¹⁰ San Francisco Department of Public Health, San Francisco, California,¹¹ Institute of Microbiology, University of Lausanne, Lausanne,² Department of Genetics and Microbiology, University of Geneva,⁵ Division of Infectious Diseases, University Hospital of Geneva, Geneva, Switzerland,⁶ Department of Social Medicine, University of Bristol, Bristol, United Kingdom⁴

Received 18 February 2004/ Accepted 2 June 2004

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 GA 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.

Supplemental material for this article may be found at http://jvi.asm.org/.

P.A. and G.B. contributed equally to this work.

This article has been cited by other articles:

• Henry, W. K., Tebas, P., Lane, H. C. (2006). Explaining, predicting, and treating HIV-associated CD4 cell loss: after 25 years still a puzzle.. JAMA 296: 1523-1525 [Full Text]  
• Pace, C., Keller, J., Nolan, D., James, I., Gaudieri, S., Moore, C., Mallal, S. (2006). Population Level Analysis of Human Immunodeficiency Virus Type 1 Hypermutation and Its Relationship with APOBEC3G and vif Genetic Variation.. J. Virol. 80: 9259-9269 [Abstract] [Full Text]  
• Speelmon, E. C., Livingston-Rosanoff, D., Li, S. S., Vu, Q., Bui, J., Geraghty, D. E., Zhao, L. P., McElrath, M. J. (2006). Genetic Association of the Antiviral Restriction Factor TRIM5{alpha} with Human Immunodeficiency Virus Type 1 Infection. J. Virol. 80: 2463-2471 [Abstract] [Full Text]  
• Turelli, P., Trono, D. (2005). Editing at the Crossroad of Innate and Adaptive Immunity. Science 307: 1061-1065 [Abstract] [Full Text]