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

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 in...

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Main Authors: 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 Hunt, Guido Silvestri
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-08-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1004345
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author 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 Hunt
Guido Silvestri
author_facet 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 Hunt
Guido Silvestri
author_sort Nichole R Klatt
collection DOAJ
description 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.
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spelling doaj-art-eef74e25784f450da0159e4e5b4488762025-08-20T03:12:34ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-08-01108e100434510.1371/journal.ppat.1004345Limited HIV infection of central memory and stem cell memory CD4+ T cells is associated with lack of progression in viremic individuals.Nichole R KlattSteven E BosingerMelicent PeckLaura E Richert-SpuhlerAnke HeigeleJillian P GileNirav PatelJessica TaaffeBoris JulgDavid CameriniCarlo TortiJeffrey N MartinSteven G DeeksElizabeth SinclairFrederick M HechtMichael M LedermanMirko PaiardiniFrank KirchhoffJason M BrenchleyPeter W HuntGuido SilvestriA 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.https://doi.org/10.1371/journal.ppat.1004345
spellingShingle 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 Hunt
Guido Silvestri
Limited HIV infection of central memory and stem cell memory CD4+ T cells is associated with lack of progression in viremic individuals.
PLoS Pathogens
title Limited HIV infection of central memory and stem cell memory CD4+ T cells is associated with lack of progression in viremic individuals.
title_full Limited HIV infection of central memory and stem cell memory CD4+ T cells is associated with lack of progression in viremic individuals.
title_fullStr Limited HIV infection of central memory and stem cell memory CD4+ T cells is associated with lack of progression in viremic individuals.
title_full_unstemmed Limited HIV infection of central memory and stem cell memory CD4+ T cells is associated with lack of progression in viremic individuals.
title_short Limited HIV infection of central memory and stem cell memory CD4+ T cells is associated with lack of progression in viremic individuals.
title_sort limited hiv infection of central memory and stem cell memory cd4 t cells is associated with lack of progression in viremic individuals
url https://doi.org/10.1371/journal.ppat.1004345
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