HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Baseline CD4+ T cell counts correlates with HIV-1 synonymous rate in HLA-B*5701 subjects with different risk of disease progression.

Abstract
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.
AuthorsMelissa M Norström, Nazle M Veras, Wei Huang, Mattia C F Proper, Jennifer Cook, Wendy Hartogensis, Frederick M Hecht, Annika C Karlsson, Annika C Karlsoon, Marco Salemi
JournalPLoS computational biology (PLoS Comput Biol) Vol. 10 Issue 9 Pg. e1003830 (Sep 2014) ISSN: 1553-7358 [Electronic] United States
PMID25187947 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • HIV Core Protein p24
  • HLA-B Antigens
  • HLA-B*57:01 antigen
  • p24 protein, Human Immunodeficiency Virus Type 1
Topics
  • Bayes Theorem
  • CD4-Positive T-Lymphocytes
  • Computational Biology
  • Disease Progression
  • HIV Core Protein p24 (classification, genetics)
  • HIV Infections (epidemiology, immunology, virology)
  • HIV-1 (genetics)
  • HLA-B Antigens
  • Humans
  • Molecular Sequence Data
  • Mutation (genetics)
  • Virus Replication (genetics)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: