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PLoS Pathog. 2014 Aug 28;10(8):e1004345. doi: 10.1371/journal.ppat.1004345. eCollection 2014.

Limited HIV infection of central memory and stem cell memory CD4+ T cells is associated with lack of progression in viremic individuals.

Author information

  • 1Department of Pharmaceutics, Washington National Primate Research Center, University of Washington, Seattle, Washington, United States of America; Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, United States of America.
  • 2Yerkes Primate Research Center, Emory Vaccine Center and Department of Pathology, Emory University, Atlanta, Georgia, United States of America.
  • 3Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
  • 4Department of Pharmaceutics, Washington National Primate Research Center, University of Washington, Seattle, Washington, United States of America.
  • 5Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
  • 6Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America.
  • 7Institute for Immunology, University of California Irvine, Irvine, California, United States of America.
  • 8Institute of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy.
  • 9Division of Infectious Diseases, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
  • 10Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, United States of America.

Abstract

A rare subset of HIV-infected individuals, designated viremic non-progressors (VNP), remain asymptomatic and maintain normal levels of CD4+ T-cells despite persistently high viremia. To identify mechanisms potentially responsible for the VNP phenotype, we compared VNPs (average >9 years of HIV infection) to HIV-infected individuals who have similar CD4+ T-cell counts and viral load, but who are likely to progress if left untreated ("putative progressors", PP), thus avoiding the confounding effect of differences related to substantial CD4+ T cell depletion. We found that VNPs, compared to PPs, had preserved levels of CD4+ stem cell memory cells (TSCM (p<0.0001), which was associated with decreased HIV infection of these cells in VNPs (r = -0.649, p = 0.019). In addition, VNPs had decreased HIV infection in CD4+ central memory (TCM) cells (p = 0.035), and the total number of TCM cells was associated with increased proliferation of memory CD4+ T cells (r = 0.733, p = 0.01). Our results suggest that, in HIV-infected VNPs, decreased infection of CD4+ TCM and TSCM, cells are involved in preservation of CD4+ T cell homeostasis and lack of disease progression despite high viremia.

PMID:
25167059
[PubMed - indexed for MEDLINE]
PMCID:
PMC4148445
Free PMC Article
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