An, Ping
Bleiber, Gabriela
Duggal, Priya
Nelson, George
May, Margaret
Mangeat, Bastien
Alobwede, Irene
Trono, Didier
Vlahov, David
Donfield, Sharyne
Goedert, James J.
Phair, John
Buchbinder, Susan
O'Brien, Stephen J.
Telenti, Amalio
Winkler, Cheryl A.
<jats:title>ABSTRACT</jats:title>
<jats:p>The cytosine deaminase APOBEC3G, in the absence of the human immunodeficiency virus type 1 (HIV-1) accessory gene HIV-1 viral infectivity factor (<jats:italic>vif</jats:italic>), 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 <jats:italic>APOBEC3G</jats:italic> 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) (<jats:italic>f</jats:italic> = 37%) and rare in European Americans (<jats:italic>f</jats:italic> < 3%) or Europeans (<jats:italic>f</jats:italic> = 5%). For AA, the variant allele 186R was strongly associated with decline in CD4 T cells (CD4 slope on square root scale: −1.86, <jats:italic>P</jats:italic> = 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 <jats:italic>APOBEC3G</jats:italic> on HIV-1 disease progression that warrants further investigation.</jats:p>
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https://sonar.ch/global/documents/182480
eng
info:eu-repo/semantics/altIdentifier/doi/10.1128/jvi.78.20.11070-11076.2004
info:eu-repo/semantics/altIdentifier/issn/0022-538X
info:eu-repo/semantics/openAccess
Journal of Virology. - American Society for Microbiology. - 2004, vol. 78, no. 20, p. 11070-11076
Immunology
Insect Science
Microbiology
Virology
APOBEC3G Genetic Variants and Their Influence on the Progression to AIDS
http://purl.org/coar/resource_type/c_6501