Dendritic cell-induced activation of latent HIV-1 provirus in actively proliferating primary T lymphocytes.

HIV-1 latency remains a formidable barrier towards virus eradication as therapeutic attempts to purge these reservoirs are so far unsuccessful. The pool of transcriptionally silent proviruses is established early in infection and persists for a lifetime, even when viral loads are suppressed below de...

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Autores principales:	Renée M van der Sluis, Thijs van Montfort, Georgios Pollakis, Rogier W Sanders, Dave Speijer, Ben Berkhout, Rienk E Jeeninga
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b40168c1079a4ba495516c81e01e3a63
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spelling	oai:doaj.org-article:b40168c1079a4ba495516c81e01e3a632021-11-18T06:05:53ZDendritic cell-induced activation of latent HIV-1 provirus in actively proliferating primary T lymphocytes.1553-73661553-737410.1371/journal.ppat.1003259https://doaj.org/article/b40168c1079a4ba495516c81e01e3a632013-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23555263/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374HIV-1 latency remains a formidable barrier towards virus eradication as therapeutic attempts to purge these reservoirs are so far unsuccessful. The pool of transcriptionally silent proviruses is established early in infection and persists for a lifetime, even when viral loads are suppressed below detection levels using anti-retroviral therapy. Upon therapy interruption the reservoir can re-establish systemic infection. Different cellular reservoirs that harbor latent provirus have been described. In this study we demonstrate that HIV-1 can also establish a silent integration in actively proliferating primary T lymphocytes. Co-culturing of these proliferating T lymphocytes with dendritic cells (DCs) activated the provirus from latency. Activation did not involve DC-mediated C-type lectin DC-SIGN signaling or TCR-stimulation but was mediated by DC-secreted component(s) and cell-cell interaction between DC and T lymphocyte that could be inhibited by blocking ICAM-1 dependent adhesion. These results imply that circulating DCs could purge HIV-1 from latency and re-initiate virus replication. Moreover, our data show that viral latency can be established early after infection and supports the idea that actively proliferating T lymphocytes with an effector phenotype contribute to the latent viral reservoir. Unraveling this physiologically relevant purging mechanism could provide useful information for the development of new therapeutic strategies that aim at the eradication of HIV-1 reservoirs.Renée M van der SluisThijs van MontfortGeorgios PollakisRogier W SandersDave SpeijerBen BerkhoutRienk E JeeningaPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 3, p e1003259 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Renée M van der Sluis Thijs van Montfort Georgios Pollakis Rogier W Sanders Dave Speijer Ben Berkhout Rienk E Jeeninga Dendritic cell-induced activation of latent HIV-1 provirus in actively proliferating primary T lymphocytes.
description	HIV-1 latency remains a formidable barrier towards virus eradication as therapeutic attempts to purge these reservoirs are so far unsuccessful. The pool of transcriptionally silent proviruses is established early in infection and persists for a lifetime, even when viral loads are suppressed below detection levels using anti-retroviral therapy. Upon therapy interruption the reservoir can re-establish systemic infection. Different cellular reservoirs that harbor latent provirus have been described. In this study we demonstrate that HIV-1 can also establish a silent integration in actively proliferating primary T lymphocytes. Co-culturing of these proliferating T lymphocytes with dendritic cells (DCs) activated the provirus from latency. Activation did not involve DC-mediated C-type lectin DC-SIGN signaling or TCR-stimulation but was mediated by DC-secreted component(s) and cell-cell interaction between DC and T lymphocyte that could be inhibited by blocking ICAM-1 dependent adhesion. These results imply that circulating DCs could purge HIV-1 from latency and re-initiate virus replication. Moreover, our data show that viral latency can be established early after infection and supports the idea that actively proliferating T lymphocytes with an effector phenotype contribute to the latent viral reservoir. Unraveling this physiologically relevant purging mechanism could provide useful information for the development of new therapeutic strategies that aim at the eradication of HIV-1 reservoirs.
format	article
author	Renée M van der Sluis Thijs van Montfort Georgios Pollakis Rogier W Sanders Dave Speijer Ben Berkhout Rienk E Jeeninga
author_facet	Renée M van der Sluis Thijs van Montfort Georgios Pollakis Rogier W Sanders Dave Speijer Ben Berkhout Rienk E Jeeninga
author_sort	Renée M van der Sluis
title	Dendritic cell-induced activation of latent HIV-1 provirus in actively proliferating primary T lymphocytes.
title_short	Dendritic cell-induced activation of latent HIV-1 provirus in actively proliferating primary T lymphocytes.
title_full	Dendritic cell-induced activation of latent HIV-1 provirus in actively proliferating primary T lymphocytes.
title_fullStr	Dendritic cell-induced activation of latent HIV-1 provirus in actively proliferating primary T lymphocytes.
title_full_unstemmed	Dendritic cell-induced activation of latent HIV-1 provirus in actively proliferating primary T lymphocytes.
title_sort	dendritic cell-induced activation of latent hiv-1 provirus in actively proliferating primary t lymphocytes.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/b40168c1079a4ba495516c81e01e3a63
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Dendritic cell-induced activation of latent HIV-1 provirus in actively proliferating primary T lymphocytes.

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