APOBEC3G Genetic Variants and Their Influence on the Progression to AIDS
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An, Ping
Basic Research Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center
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Bleiber, Gabriela
Institute of Microbiology, University of Lausanne, Lausanne
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Duggal, Priya
Inherited Disease Research Branch, National Human Genome Research Institute
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Nelson, George
Basic Research Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center
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May, Margaret
Department of Social Medicine, University of Bristol, Bristol, United Kingdom
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Mangeat, Bastien
Department of Genetics and Microbiology, University of Geneva
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Alobwede, Irene
Division of Infectious Diseases, University Hospital of Geneva, Geneva, Switzerland
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Trono, Didier
Department of Genetics and Microbiology, University of Geneva
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Vlahov, David
Johns Hopkins University Bloomberg School of Public Health, Baltimore
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Donfield, Sharyne
Rho Inc., Chapel Hill, North Carolina
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Goedert, James J.
Viral Epidemiology Branch, National Cancer Institute, Bethesda, Maryland
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Phair, John
Fineberg School of Medicine, Northwestern University, Comprehensive AIDS Center, Chicago, Illinois
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Buchbinder, Susan
San Francisco Department of Public Health, San Francisco, California
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O'Brien, Stephen J.
Laboratory of Genomic Diversity, National Cancer Institute, Frederick
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Telenti, Amalio
Institute of Microbiology, University of Lausanne, Lausanne
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Winkler, Cheryl A.
Basic Research Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center
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Published in:
- Journal of Virology. - American Society for Microbiology. - 2004, vol. 78, no. 20, p. 11070-11076
English
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.
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Language
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Open access status
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bronze
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Identifiers
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Persistent URL
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https://sonar.ch/global/documents/182480
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