Limited HIV Infection of Central Memory and Stem Cell Memory CD4+ T Cells Is Associated with Lack of Progression in Viremic Individuals

Nichole R. Klatt, Steven E. Bosinger, Melicent Peck, Laura E. Richert-Spuhler, Anke Heigele, Jillian P. Gile, Nirav Patel, Jessica Taaffe, Boris Julg, David Camerini, Carlo Torti, Jeffrey N. Martin, Steven G. Deeks, Elizabeth Sinclair, Frederick M. Hecht, Michael M. Lederman, Mirko Paiardini, Frank Kirchhoff, Jason M. Brenchley, Peter W. HuntGuido Silvestri

Research output: Contribution to journalArticle

51 Scopus citations

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.

Original languageEnglish (US)
Article numbere1004345
JournalPLoS pathogens
Volume10
Issue number8
DOIs
StatePublished - Aug 28 2014

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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    Klatt, N. R., Bosinger, S. E., Peck, M., Richert-Spuhler, L. E., Heigele, A., Gile, J. P., Patel, N., Taaffe, J., Julg, B., Camerini, D., Torti, C., Martin, J. N., Deeks, S. G., Sinclair, E., Hecht, F. M., Lederman, M. M., Paiardini, M., Kirchhoff, F., Brenchley, J. M., ... Silvestri, G. (2014). Limited HIV Infection of Central Memory and Stem Cell Memory CD4+ T Cells Is Associated with Lack of Progression in Viremic Individuals. PLoS pathogens, 10(8), [e1004345]. https://doi.org/10.1371/journal.ppat.1004345