APOBEC3G genetic variants and their influence on the progression to AIDS.

Détails

ID Serval
serval:BIB_F42175272A94
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
APOBEC3G genetic variants and their influence on the progression to AIDS.
Périodique
Journal of virology
Auteur(s)
An P., Bleiber G., Duggal P., Nelson G., May M., Mangeat B., Alobwede I., Trono D., Vlahov D., Donfield S., Goedert J.J., Phair J., Buchbinder S., O'Brien S.J., Telenti A., Winkler C.A.
ISSN
0022-538X
Statut éditorial
Publié
Date de publication
2004
Peer-reviewed
Oui
Volume
78
Numéro
20
Pages
11070-6
Langue
anglais
Notes
Publication types: Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. - Publication Status: ppublish
Résumé
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.
Mots-clé
African Continental Ancestry Group, Cell Line, Cohort Studies, Cytidine Deaminase, Disease Progression, Europe, European Continental Ancestry Group, Genetic Variation, HIV Infections, HIV-1, Haplotypes, Humans, Nucleoside Deaminases, Polymorphism, Single Nucleotide, Proteins, Repressor Proteins, United States
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 15:45
Dernière modification de la notice
09/05/2019 3:27
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