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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-09-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC4154639?pdf=render |
| _version_ | 1811220666064568320 |
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| author | Melissa M Norström Nazle M Veras Wei Huang Mattia C F Proper Jennifer Cook Wendy Hartogensis Frederick M Hecht Annika C Karlsson Marco Salemi |
| author_facet | Melissa M Norström Nazle M Veras Wei Huang Mattia C F Proper Jennifer Cook Wendy Hartogensis Frederick M Hecht Annika C Karlsson Marco Salemi |
| author_sort | Melissa M Norström |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T07:45:45Z |
| format | Article |
| id | doaj.art-47bac434fb8a4b59adc4bc1940044c14 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-04-12T07:45:45Z |
| publishDate | 2014-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-47bac434fb8a4b59adc4bc1940044c142022-12-22T03:41:43ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582014-09-01109e100383010.1371/journal.pcbi.1003830Baseline CD4+ T cell counts correlates with HIV-1 synonymous rate in HLA-B*5701 subjects with different risk of disease progression.Melissa M NorströmNazle M VerasWei HuangMattia C F ProperJennifer CookWendy HartogensisFrederick M HechtAnnika C KarlssonMarco SalemiHLA-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.http://europepmc.org/articles/PMC4154639?pdf=render |
| spellingShingle | Melissa M Norström Nazle M Veras Wei Huang Mattia C F Proper Jennifer Cook Wendy Hartogensis Frederick M Hecht Annika C Karlsson Marco Salemi Baseline CD4+ T cell counts correlates with HIV-1 synonymous rate in HLA-B*5701 subjects with different risk of disease progression. PLoS Computational Biology |
| 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 |
| url | http://europepmc.org/articles/PMC4154639?pdf=render |
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