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Global Database-Driven Assessment of HIV-1 Adaptation to the Immune Repertoires of Human Populations.

ABSTRACT: Associations between HIV-1 cytotoxic T lymphocyte (CTL) escape mutations and their restricting human leukocyte antigen (HLA) alleles imply that HIV could adapt to divergent HLA repertoires of human populations globally. Using publicly available databases, we examine the relationship between the frequencies of 19 experimentally validated CTL escape mutations in HIV-1 reverse transcriptase and their restricting HLA alleles in 59 countries. From these extensive data, we find evidence of differential HIV adaptations to human populations at only a limited number of the studied epitope sites.

SUBMITTER: Karakas A

PROVIDER: S-EPMC4580167 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Global Database-Driven Assessment of HIV-1 Adaptation to the Immune Repertoires of Human Populations.

Karakas Aram A Brumme Zabrina L ZL Poon Art F Y AF

Journal of virology 20150805 20

Associations between HIV-1 cytotoxic T lymphocyte (CTL) escape mutations and their restricting human leukocyte antigen (HLA) alleles imply that HIV could adapt to divergent HLA repertoires of human populations globally. Using publicly available databases, we examine the relationship between the frequencies of 19 experimentally validated CTL escape mutations in HIV-1 reverse transcriptase and their restricting HLA alleles in 59 countries. From these extensive data, we find evidence of differentia ...[more]

PMID: 26246562

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Project description:BACKGROUND: Cytotoxic T-Lymphocyte (CTL) response drives the evolution of HIV-1 at a host-level by selecting HLA-restricted escape mutations. Dissecting the dynamics of these escape mutations at a population-level would help to understand how HLA-mediated selection drives the evolution of HIV-1. METHODOLOGY/PRINCIPAL FINDINGS: We undertook a study of the dynamics of HIV-1 CTL-escape mutations by analyzing through statistical approaches and phylogenetic methods the viral gene gag sequenced in plasma samples collected between the years 1987 and 2006 from 302 drug-naïve HIV-positive patients. By applying logistic regression models and after performing correction for multiple test, we identified 22 potential CTL-escape mutations (p-value<0.05; q-value<0.2); 10 of these associations were confirmed in samples biologically independent by a Bayesian Markov Chain Monte-Carlo method. Analyzing their prevalence back in time we found that escape mutations that are the consensus residue in samples collected after 2003 have actually significantly increased in time in one of either B or F subtype until becoming the most frequent residue, while dominating the other viral subtype. Their estimated prevalence in the viral subtype they did not dominate was lower than 30% for the majority of samples collected at the end of the 80's. In addition, when screening the entire viral region, we found that the 75% of positions significantly changing in time (p<0.05) were located within known CTL epitopes. CONCLUSIONS: Across HIV Gag protein, the rise of polymorphisms from independent origin during the last twenty years of epidemic in our setting was related to an association with an HLA allele. The fact that these mutations accumulated in one of either B or F subtypes have also dominated the other subtype shows how this selection might be causing a convergence of viral subtypes to variants which are more likely to evade the immune response of the population where they circulate.

Dataset Information

Global Database-Driven Assessment of HIV-1 Adaptation to the Immune Repertoires of Human Populations.

Publications

Global Database-Driven Assessment of HIV-1 Adaptation to the Immune Repertoires of Human Populations.

Similar Datasets

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