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
Institution
Titre
APOBEC3G genetic variants and their influence on the progression to AIDS.
Périodique
Journal of virology
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
20/08/2019 17:21