title: Limited HIV infection of central memory and stem cell memory CD4+ T cells is associated with lack of progression in viremic individuals.
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.
authors.affiliation: Department 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.
authors.forename: Nichole R
authors.initials: NR
authors.lastname: Klatt
authors.affiliation: Yerkes Primate Research Center, Emory Vaccine Center and Department of Pathology, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Bosinger
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Melicent
authors.initials: M
authors.lastname: Peck
authors.affiliation: Department of Pharmaceutics, Washington National Primate Research Center, University of Washington, Seattle, Washington, United States of America.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Richert-Spuhler
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Heigele
authors.affiliation: Department of Pharmaceutics, Washington National Primate Research Center, University of Washington, Seattle, Washington, United States of America.
authors.forename: Jillian P
authors.initials: JP
authors.lastname: Gile
authors.affiliation: Yerkes Primate Research Center, Emory Vaccine Center and Department of Pathology, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Nirav
authors.initials: N
authors.lastname: Patel
authors.affiliation: Yerkes Primate Research Center, Emory Vaccine Center and Department of Pathology, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Jessica
authors.initials: J
authors.lastname: Taaffe
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America.
authors.forename: Boris
authors.initials: B
authors.lastname: Julg
authors.affiliation: Institute for Immunology, University of California Irvine, Irvine, California, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Camerini
authors.affiliation: Institute of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Torti
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sinclair
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
authors.affiliation: Division of Infectious Diseases, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.affiliation: Yerkes Primate Research Center, Emory Vaccine Center and Department of Pathology, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Mirko
authors.initials: M
authors.lastname: Paiardini
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
authors.affiliation: Yerkes Primate Research Center, Emory Vaccine Center and Department of Pathology, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002469:Cell Separation; D004279:DNA, Viral / Q000032:analysis; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D020411:Oligonucleotide Array Sequence Analysis; D013234:Stem Cells / Q000276:immunology / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000821:virology; D019562:Viral Load; D014766:Viremia / Q000276:immunology* / Q000821:virology
chemical_list: D004279:DNA, Viral