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

• Type of Material: Article
• Authors: Nichole R. Klatt, University of Washington; Steven Bosinger, Emory University; Melicent Peck, University of California San Francisco; Laura E. Richert-Spuhler, University of Washington; Anke Heigele, University of Ulm; Jillian P. Gile, University of Washington; Nirav Patel, Emory University; Jessica Taaffe, Emory University; Boris Julg, Massachusetts Institute of Technology; David Camerini, University of California Irvine; Carlo Torti, University of Brescia; Jeffrey N. Martin, University of California San Francisco; Steven G. Deeks, University of California San Francisco; Elizabeth Sinclair, University of California San Francisco; Frederick M. Hecht, University of California San Francisco; Michael M. Lederman, Case Western Reserve University; Mirko Paiardini, Emory University; Frank Kirchhoff, University of Ulm; Jason M. Brenchley, National Institutes of Health; Peter W. Hunt, University of California San Francisco; Guido Silvestri, Emory University
• Language: English
• Date: 2014-08-01
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
• License: Creative Commons Creative Commons CC0 1.0 Universal
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.ppat.1004345
• Title of Journal or Parent Work: PLoS Pathogens
• ISSN: 1553-7366
• Volume: 10
• Issue: 8
• Start Page: e1004345
• End Page: e1004345
• Grant/Funding Information: This work was supported by: the Hector Foundation and the Deutsche Forschungsgemeinschaft (Leibniz award to FK), and NIH/NIAID grants P01 AI 076174 (Cleveland Immunopathogensis Program), R01 AI110334 (MPa), K22 AI098440 (NRK) and in part by University of Washington Center for AIDS Research, P30 AI027757 and University of California San Francisco Center for AIDS Research, P30 AI027763 and R24 AI067039.
• Keywords: Cell enumeration techniques; Cytotoxic T cells; DISEASE; Gene expression; HIV infections; SIV INFECTION; Life Sciences & Biomedicine; Microbiology; IMMUNODEFICIENCY-VIRUS CONTROLLERS; RHESUS MACAQUES; PERSISTENCE; IMMUNE ACTIVATION; Memory; Science & Technology; ANTIRETROVIRAL THERAPY; HIV; Parasitology; T cells; Memory T cells; TYPE-1 INFECTION; SOOTY MANGABEYS; Virology; RESPONSES
• Research Categories: Health Sciences, Immunology; Biology, Virology; Biology, Microbiology

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.