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Baseline CD4(+) T Cell Counts Correlates with HIV-1 Synonymous Rate in HLA-B*5701 Subjects with Different Risk of Disease Progression

HLA-B*5701 is the host factor most strongly associated with slow HIV-1 disease progression, although risk of progression may vary among patients carrying this allele. The interplay between HIV-1 evolutionary rate variation and risk of progression to AIDS in HLA-B*5701 subjects was studied using long...

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Autores principales: Norström, Melissa M., Veras, Nazle M., Huang, Wei, Proper, Mattia C. F., Cook, Jennifer, Hartogensis, Wendy, Hecht, Frederick M., Karlsoon, Annika C., Salemi, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154639/
https://www.ncbi.nlm.nih.gov/pubmed/25187947
http://dx.doi.org/10.1371/journal.pcbi.1003830
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author Norström, Melissa M.
Veras, Nazle M.
Huang, Wei
Proper, Mattia C. F.
Cook, Jennifer
Hartogensis, Wendy
Hecht, Frederick M.
Karlsoon, Annika C.
Salemi, Marco
author_facet Norström, Melissa M.
Veras, Nazle M.
Huang, Wei
Proper, Mattia C. F.
Cook, Jennifer
Hartogensis, Wendy
Hecht, Frederick M.
Karlsoon, Annika C.
Salemi, Marco
author_sort Norström, Melissa M.
collection PubMed
description HLA-B*5701 is the host factor most strongly associated with slow HIV-1 disease progression, although risk of progression may vary among patients carrying this allele. The interplay between HIV-1 evolutionary rate variation and risk of progression to AIDS in HLA-B*5701 subjects was studied using longitudinal viral sequences from high-risk progressors (HRPs) and low-risk progressors (LRPs). Posterior distributions of HIV-1 genealogies assuming a Bayesian relaxed molecular clock were used to estimate the absolute rates of nonsynonymous and synonymous substitutions for different set of branches. Rates of viral evolution, as well as in vitro viral replication capacity assessed using a novel phenotypic assay, were correlated with various clinical parameters. HIV-1 synonymous substitution rates were significantly lower in LRPs than HRPs, especially for sets of internal branches. The viral population infecting LRPs was also characterized by a slower increase in synonymous divergence over time. This pattern did not correlate to differences in viral fitness, as measured by in vitro replication capacity, nor could be explained by differences among subjects in T cell activation or selection pressure. Interestingly, a significant inverse correlation was found between baseline CD4(+) T cell counts and mean HIV-1 synonymous rate (which is proportional to the viral replication rate) along branches representing viral lineages successfully propagating through time up to the last sampled time point. The observed lower replication rate in HLA-B*5701 subjects with higher baseline CD4(+) T cell counts provides a potential model to explain differences in risk of disease progression among individuals carrying this allele.
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spelling pubmed-41546392014-09-08 Baseline CD4(+) T Cell Counts Correlates with HIV-1 Synonymous Rate in HLA-B*5701 Subjects with Different Risk of Disease Progression Norström, Melissa M. Veras, Nazle M. Huang, Wei Proper, Mattia C. F. Cook, Jennifer Hartogensis, Wendy Hecht, Frederick M. Karlsoon, Annika C. Salemi, Marco PLoS Comput Biol Research Article HLA-B*5701 is the host factor most strongly associated with slow HIV-1 disease progression, although risk of progression may vary among patients carrying this allele. The interplay between HIV-1 evolutionary rate variation and risk of progression to AIDS in HLA-B*5701 subjects was studied using longitudinal viral sequences from high-risk progressors (HRPs) and low-risk progressors (LRPs). Posterior distributions of HIV-1 genealogies assuming a Bayesian relaxed molecular clock were used to estimate the absolute rates of nonsynonymous and synonymous substitutions for different set of branches. Rates of viral evolution, as well as in vitro viral replication capacity assessed using a novel phenotypic assay, were correlated with various clinical parameters. HIV-1 synonymous substitution rates were significantly lower in LRPs than HRPs, especially for sets of internal branches. The viral population infecting LRPs was also characterized by a slower increase in synonymous divergence over time. This pattern did not correlate to differences in viral fitness, as measured by in vitro replication capacity, nor could be explained by differences among subjects in T cell activation or selection pressure. Interestingly, a significant inverse correlation was found between baseline CD4(+) T cell counts and mean HIV-1 synonymous rate (which is proportional to the viral replication rate) along branches representing viral lineages successfully propagating through time up to the last sampled time point. The observed lower replication rate in HLA-B*5701 subjects with higher baseline CD4(+) T cell counts provides a potential model to explain differences in risk of disease progression among individuals carrying this allele. Public Library of Science 2014-09-04 /pmc/articles/PMC4154639/ /pubmed/25187947 http://dx.doi.org/10.1371/journal.pcbi.1003830 Text en © 2014 Norström et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Norström, Melissa M.
Veras, Nazle M.
Huang, Wei
Proper, Mattia C. F.
Cook, Jennifer
Hartogensis, Wendy
Hecht, Frederick M.
Karlsoon, Annika C.
Salemi, Marco
Baseline CD4(+) T Cell Counts Correlates with HIV-1 Synonymous Rate in HLA-B*5701 Subjects with Different Risk of Disease Progression
title Baseline CD4(+) T Cell Counts Correlates with HIV-1 Synonymous Rate in HLA-B*5701 Subjects with Different Risk of Disease Progression
title_full Baseline CD4(+) T Cell Counts Correlates with HIV-1 Synonymous Rate in HLA-B*5701 Subjects with Different Risk of Disease Progression
title_fullStr Baseline CD4(+) T Cell Counts Correlates with HIV-1 Synonymous Rate in HLA-B*5701 Subjects with Different Risk of Disease Progression
title_full_unstemmed Baseline CD4(+) T Cell Counts Correlates with HIV-1 Synonymous Rate in HLA-B*5701 Subjects with Different Risk of Disease Progression
title_short Baseline CD4(+) T Cell Counts Correlates with HIV-1 Synonymous Rate in HLA-B*5701 Subjects with Different Risk of Disease Progression
title_sort baseline cd4(+) t cell counts correlates with hiv-1 synonymous rate in hla-b*5701 subjects with different risk of disease progression
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154639/
https://www.ncbi.nlm.nih.gov/pubmed/25187947
http://dx.doi.org/10.1371/journal.pcbi.1003830
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