Directly infected resting CD4+T cells can produce HIV Gag without spreading infection in a model of HIV latency.

Despite the effectiveness of highly active antiretroviral therapy (HAART) in treating individuals infected with HIV, HAART is not a cure. A latent reservoir, composed mainly of resting CD4+T cells, drives viral rebound once therapy is stopped. Understanding the formation and maintenance of latently...

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Autores principales:	Matthew J Pace, Erin H Graf, Luis M Agosto, Angela M Mexas, Frances Male, Troy Brady, Frederic D Bushman, Una O'Doherty
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/dbccde35766d4ad09774f366e3f2ac9f
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spelling	oai:doaj.org-article:dbccde35766d4ad09774f366e3f2ac9f2021-11-18T06:04:11ZDirectly infected resting CD4+T cells can produce HIV Gag without spreading infection in a model of HIV latency.1553-73661553-737410.1371/journal.ppat.1002818https://doaj.org/article/dbccde35766d4ad09774f366e3f2ac9f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22911005/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Despite the effectiveness of highly active antiretroviral therapy (HAART) in treating individuals infected with HIV, HAART is not a cure. A latent reservoir, composed mainly of resting CD4+T cells, drives viral rebound once therapy is stopped. Understanding the formation and maintenance of latently infected cells could provide clues to eradicating this reservoir. However, there have been discrepancies regarding the susceptibility of resting cells to HIV infection in vitro and in vivo. As we have previously shown that resting CD4+T cells are susceptible to HIV integration, we asked whether these cells were capable of producing viral proteins and if so, why resting cells were incapable of supporting productive infection. To answer this question, we spinoculated resting CD4+T cells with or without prior stimulation, and measured integration, transcription, and translation of viral proteins. We found that resting cells were capable of producing HIV Gag without supporting spreading infection. This block corresponded with low HIV envelope levels both at the level of protein and RNA and was not an artifact of spinoculation. The defect was reversed upon stimulation with IL-7 or CD3/28 beads. Thus, a population of latent cells can produce viral proteins without resulting in spreading infection. These results have implications for therapies targeting the latent reservoir and suggest that some latent cells could be cleared by a robust immune response.Matthew J PaceErin H GrafLuis M AgostoAngela M MexasFrances MaleTroy BradyFrederic D BushmanUna O'DohertyPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 7, p e1002818 (2012)
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 Matthew J Pace Erin H Graf Luis M Agosto Angela M Mexas Frances Male Troy Brady Frederic D Bushman Una O'Doherty Directly infected resting CD4+T cells can produce HIV Gag without spreading infection in a model of HIV latency.
description	Despite the effectiveness of highly active antiretroviral therapy (HAART) in treating individuals infected with HIV, HAART is not a cure. A latent reservoir, composed mainly of resting CD4+T cells, drives viral rebound once therapy is stopped. Understanding the formation and maintenance of latently infected cells could provide clues to eradicating this reservoir. However, there have been discrepancies regarding the susceptibility of resting cells to HIV infection in vitro and in vivo. As we have previously shown that resting CD4+T cells are susceptible to HIV integration, we asked whether these cells were capable of producing viral proteins and if so, why resting cells were incapable of supporting productive infection. To answer this question, we spinoculated resting CD4+T cells with or without prior stimulation, and measured integration, transcription, and translation of viral proteins. We found that resting cells were capable of producing HIV Gag without supporting spreading infection. This block corresponded with low HIV envelope levels both at the level of protein and RNA and was not an artifact of spinoculation. The defect was reversed upon stimulation with IL-7 or CD3/28 beads. Thus, a population of latent cells can produce viral proteins without resulting in spreading infection. These results have implications for therapies targeting the latent reservoir and suggest that some latent cells could be cleared by a robust immune response.
format	article
author	Matthew J Pace Erin H Graf Luis M Agosto Angela M Mexas Frances Male Troy Brady Frederic D Bushman Una O'Doherty
author_facet	Matthew J Pace Erin H Graf Luis M Agosto Angela M Mexas Frances Male Troy Brady Frederic D Bushman Una O'Doherty
author_sort	Matthew J Pace
title	Directly infected resting CD4+T cells can produce HIV Gag without spreading infection in a model of HIV latency.
title_short	Directly infected resting CD4+T cells can produce HIV Gag without spreading infection in a model of HIV latency.
title_full	Directly infected resting CD4+T cells can produce HIV Gag without spreading infection in a model of HIV latency.
title_fullStr	Directly infected resting CD4+T cells can produce HIV Gag without spreading infection in a model of HIV latency.
title_full_unstemmed	Directly infected resting CD4+T cells can produce HIV Gag without spreading infection in a model of HIV latency.
title_sort	directly infected resting cd4+t cells can produce hiv gag without spreading infection in a model of hiv latency.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/dbccde35766d4ad09774f366e3f2ac9f
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Directly infected resting CD4+T cells can produce HIV Gag without spreading infection in a model of HIV latency.

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