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CD32(+)CD4(+) T Cells Are Highly Enriched for HIV DNA and Can Support Transcriptional Latency

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 a...

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Autores principales: Darcis, Gilles, Kootstra, Neeltje A., Hooibrink, Berend, van Montfort, Thijs, Maurer, Irma, Groen, Kevin, Jurriaans, Suzanne, Bakker, Margreet, van Lint, Carine, Berkhout, Ben, Pasternak, Alexander O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050565/
https://www.ncbi.nlm.nih.gov/pubmed/32075737
http://dx.doi.org/10.1016/j.celrep.2020.01.071
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author Darcis, Gilles
Kootstra, Neeltje A.
Hooibrink, Berend
van Montfort, Thijs
Maurer, Irma
Groen, Kevin
Jurriaans, Suzanne
Bakker, Margreet
van Lint, Carine
Berkhout, Ben
Pasternak, Alexander O.
author_facet Darcis, Gilles
Kootstra, Neeltje A.
Hooibrink, Berend
van Montfort, Thijs
Maurer, Irma
Groen, Kevin
Jurriaans, Suzanne
Bakker, Margreet
van Lint, Carine
Berkhout, Ben
Pasternak, Alexander O.
author_sort Darcis, Gilles
collection PubMed
description 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.
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spelling pubmed-70505652020-03-02 CD32(+)CD4(+) T Cells Are Highly Enriched for HIV DNA and Can Support Transcriptional Latency Darcis, Gilles Kootstra, Neeltje A. Hooibrink, Berend van Montfort, Thijs Maurer, Irma Groen, Kevin Jurriaans, Suzanne Bakker, Margreet van Lint, Carine Berkhout, Ben Pasternak, Alexander O. Cell Rep Article 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. 2020-02-18 /pmc/articles/PMC7050565/ /pubmed/32075737 http://dx.doi.org/10.1016/j.celrep.2020.01.071 Text en This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Darcis, Gilles
Kootstra, Neeltje A.
Hooibrink, Berend
van Montfort, Thijs
Maurer, Irma
Groen, Kevin
Jurriaans, Suzanne
Bakker, Margreet
van Lint, Carine
Berkhout, Ben
Pasternak, Alexander O.
CD32(+)CD4(+) T Cells Are Highly Enriched for HIV DNA and Can Support Transcriptional Latency
title CD32(+)CD4(+) T Cells Are Highly Enriched for HIV DNA and Can Support Transcriptional Latency
title_full CD32(+)CD4(+) T Cells Are Highly Enriched for HIV DNA and Can Support Transcriptional Latency
title_fullStr CD32(+)CD4(+) T Cells Are Highly Enriched for HIV DNA and Can Support Transcriptional Latency
title_full_unstemmed CD32(+)CD4(+) T Cells Are Highly Enriched for HIV DNA and Can Support Transcriptional Latency
title_short CD32(+)CD4(+) T Cells Are Highly Enriched for HIV DNA and Can Support Transcriptional Latency
title_sort cd32(+)cd4(+) t cells are highly enriched for hiv dna and can support transcriptional latency
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050565/
https://www.ncbi.nlm.nih.gov/pubmed/32075737
http://dx.doi.org/10.1016/j.celrep.2020.01.071
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