Polymorphisms in toll-like receptor 4 and toll-like receptor 9 influence viral load in a seroincident cohort of HIV-1-infected individuals.

Détails

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_BBC1EAB86159
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Polymorphisms in toll-like receptor 4 and toll-like receptor 9 influence viral load in a seroincident cohort of HIV-1-infected individuals.
Périodique
AIDS
Auteur(s)
Pine Samuel O., McElrath M. Juliana , Bochud Pierre-Yves
ISSN
1473-5571[electronic]
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
23
Numéro
18
Pages
2387-2395
Langue
anglais
Résumé
OBJECTIVES: Toll-like receptors (TLRs) are innate immune sensors that are integral to resisting chronic and opportunistic infections. Mounting evidence implicates TLR polymorphisms in susceptibilities to various infectious diseases, including HIV-1. We investigated the impact of TLR single nucleotide polymorphisms (SNPs) on clinical outcome in a seroincident cohort of HIV-1-infected volunteers. DESIGN: We analyzed TLR SNPs in 201 antiretroviral treatment-naive HIV-1-infected volunteers from a longitudinal seroincident cohort with regular follow-up intervals (median follow-up 4.2 years, interquartile range 4.4). Participants were stratified into two groups according to either disease progression, defined as peripheral blood CD4(+) T-cell decline over time, or peak and setpoint viral load. METHODS: Haplotype tagging SNPs from TLR2, TLR3, TLR4, and TLR9 were detected by mass array genotyping, and CD4(+) T-cell counts and viral load measurements were determined prior to antiretroviral therapy initiation. The association of TLR haplotypes with viral load and rapid progression was assessed by multivariate regression models using age and sex as covariates. RESULTS: Two TLR4 SNPs in strong linkage disequilibrium [1063 A/G (D299G) and 1363 C/T (T399I)] were more frequent among individuals with high peak viral load compared with low/moderate peak viral load (odds ratio 6.65, 95% confidence interval 2.19-20.46, P < 0.001; adjusted P = 0.002 for 1063 A/G). In addition, a TLR9 SNP previously associated with slow progression was found less frequently among individuals with high viral setpoint compared with low/moderate setpoint (odds ratio 0.29, 95% confidence interval 0.13-0.65, P = 0.003, adjusted P = 0.04). CONCLUSION: This study suggests a potentially new role for TLR4 polymorphisms in HIV-1 peak viral load and confirms a role for TLR9 polymorphisms in disease progression.
Mots-clé
HIV-1, HIV genetics, HIV immunology, Innate Immunity, Single Nucleotide Polymorphism, Toll-Like Receptor 4, Toll-Like Receptor 9, Respiratory Syncytial Virus, Primary HIV-Infection, Systemic-Lupus-Erythematosus, Long-Term Nonprogressors, T-Cell Exhaustion, Disease Progression, Type-1 Infection, Bactericidal Lectin, TLR4 Polymorphisms, Prevalent-Cohort
Pubmed
Web of science
Création de la notice
15/12/2009 17:38
Dernière modification de la notice
20/08/2019 16:29
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