Article (Scientific journals)
CD32+CD4+ T Cells Are Highly Enriched for HIV DNA and Can Support Transcriptional Latency
Darcis, Gilles; Kootstra, Neeltje A.; Hooibrink, Berend et al.
2020In Cell Reports, 30 (7), p. 2284-2296.e3
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Keywords :
CD32; HIV cure; HIV latency; HIV persistence; HIV reservoir; CD32 antigen; Article; CD4+ T lymphocyte; DNA transcription; Human immunodeficiency virus infection
Abstract :
[en] The HIV latent reservoir forms the major hurdle to an HIV cure. The discovery of CD32 as marker of this reservoir has aroused much interest, but subsequent reports have challenged this finding. Here, we observe a positive correlation between the percentages of CD32+ cells among CD4+ T cells of aviremic cART-treated, HIV-infected individuals and their HIV DNA loads in peripheral blood. Moreover, optimization of the CD32+CD4+ T cell purification protocol reveals prominent enrichment for HIV DNA (mean, 292-fold) in these cells. However, no enrichment for HIV RNA is observed in CD32+CD4+ cells, yielding significantly reduced HIV RNA/DNA ratios. Furthermore, HIV proviruses in CD32+CD4+ cells can be reactivated ex vivo to produce virus, strongly suggesting that these cells support HIV transcriptional latency. Our results underscore the importance of isolating pure, bona fide CD32+CD4+ T cells for future studies and indicate that CD32 remains a promising candidate marker of the HIV reservoir. © 2020 The Author(s)CD32a was recently proposed to mark the HIV reservoir, but this finding was subsequently challenged. By using a sequential cell-sorting protocol to purify bona fide CD32+CD4+ cells, Darcis et al. demonstrate HIV DNA enrichment and ex vivo reactivation-mediated virus production in these cells, reinforcing CD32 as an HIV reservoir marker. © 2020 The Author(s)
Disciplines :
Immunology & infectious disease
Author, co-author :
Darcis, Gilles ;  Université de Liège - ULiège > I3-Cellular and Molecular Immunology
Kootstra, Neeltje A.;  Laboratory of Viral Immune Pathogenesis, Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
Hooibrink, Berend;  Department of Cell Biology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
van Montfort, Thijs;  Laboratory of Experimental Virology, Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
Maurer, Irma;  Laboratory of Viral Immune Pathogenesis, Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
Groen, Kevin;  Laboratory of Experimental Virology, Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
Jurriaans, Suzanne;  Laboratory of Clinical Virology, Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
Bakker, Margreet;  Laboratory of Experimental Virology, Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
van Lint, Carine;  Service of Molecular Virology, Département de Biologie Moléculaire (DBM), Université Libre de Bruxelles (ULB), Gosselies, Belgium
Berkhout, Ben;  Laboratory of Experimental Virology, Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
Pasternak, Alexander O.;  Laboratory of Experimental Virology, Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
Language :
English
Title :
CD32+CD4+ T Cells Are Highly Enriched for HIV DNA and Can Support Transcriptional Latency
Publication date :
2020
Journal title :
Cell Reports
eISSN :
2211-1247
Publisher :
Elsevier B.V.
Volume :
30
Issue :
7
Pages :
2284-2296.e3
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
Fonds Léon Fredericq [BE]
NIH - National Institutes of Health [US-MD] [US-MD]
NIAID - National Institute of Allergy and Infectious Diseases [US-MD] [US-MD]
FRB - Fondation Roi Baudouin [BE]
Rotary International [US-IL] [US-IL]
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since 13 May 2020

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