PMID- 25187947
OWN - NLM
STAT- MEDLINE
DCOM- 20151130
LR  - 20211021
IS  - 1553-7358 (Electronic)
IS  - 1553-734X (Print)
IS  - 1553-734X (Linking)
VI  - 10
IP  - 9
DP  - 2014 Sep
TI  - Baseline CD4+ T cell counts correlates with HIV-1 synonymous rate in HLA-B*5701 
      subjects with different risk of disease progression.
PG  - e1003830
LID - 10.1371/journal.pcbi.1003830 [doi]
LID - e1003830
AB  - 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.
FAU - Norstrom, Melissa M
AU  - Norstrom MM
AD  - Division of Clinical Microbiology & Center for HIV Research, Department of 
      Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
FAU - Veras, Nazle M
AU  - Veras NM
AD  - Department of Pathology, Immunology and Laboratory Medicine & Emerging Pathogens 
      Institute, University of Florida, Gainesville, Florida, United States of America.
FAU - Huang, Wei
AU  - Huang W
AD  - Monogram Biosciences Inc., South San Francisco, California, United States of 
      America.
FAU - Proper, Mattia C F
AU  - Proper MC
AD  - Centre for Health Informatics, Institute of Population Health, University of 
      Manchester, Manchester, United Kingdom.
FAU - Cook, Jennifer
AU  - Cook J
AD  - Monogram Biosciences Inc., South San Francisco, California, United States of 
      America.
FAU - Hartogensis, Wendy
AU  - Hartogensis W
AD  - UCSF Positive Health Program, San Francisco General Hospital, University of 
      California, San Francisco, San Francisco, California, United States of America.
FAU - Hecht, Frederick M
AU  - Hecht FM
AD  - UCSF Positive Health Program, San Francisco General Hospital, University of 
      California, San Francisco, San Francisco, California, United States of America.
FAU - Karlsson, Annika C
AU  - Karlsson AC
FAU - Salemi, Marco
AU  - Salemi M
AD  - Department of Pathology, Immunology and Laboratory Medicine & Emerging Pathogens 
      Institute, University of Florida, Gainesville, Florida, United States of America.
LA  - eng
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GR  - K24 AT007827/AT/NCCIH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140904
PL  - United States
TA  - PLoS Comput Biol
JT  - PLoS computational biology
JID - 101238922
RN  - 0 (HIV Core Protein p24)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B*57:01 antigen)
RN  - 0 (p24 protein, Human Immunodeficiency Virus Type 1)
SB  - IM
EIN - PLoS Comput Biol. 2014 Nov;10(11):e1004000. Karlsoon, Annika C [corrected to 
      Karlsson, Annika C]
MH  - Bayes Theorem
MH  - *CD4-Positive T-Lymphocytes
MH  - Computational Biology
MH  - Disease Progression
MH  - HIV Core Protein p24/classification/genetics
MH  - HIV Infections/epidemiology/*immunology/*virology
MH  - HIV-1/*genetics
MH  - *HLA-B Antigens
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutation/genetics
MH  - Virus Replication/genetics
PMC - PMC4154639
COIS- Wei Huang and Jennifer Cook are employees of Monogram Biosciences Inc. All other 
      authors have declared that no competing interests exist.
EDAT- 2014/09/05 06:00
MHDA- 2015/12/15 06:00
PMCR- 2014/09/04
CRDT- 2014/09/05 06:00
PHST- 2014/04/28 00:00 [received]
PHST- 2014/07/28 00:00 [accepted]
PHST- 2014/09/05 06:00 [entrez]
PHST- 2014/09/05 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2014/09/04 00:00 [pmc-release]
AID - PCOMPBIOL-D-14-00745 [pii]
AID - 10.1371/journal.pcbi.1003830 [doi]
PST - epublish
SO  - PLoS Comput Biol. 2014 Sep 4;10(9):e1003830. doi: 10.1371/journal.pcbi.1003830. 
      eCollection 2014 Sep.