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Persistence of an intact HIV reservoir in phenotypically naive T cells

Despite the efficacy of antiretroviral therapy (ART), HIV persists in a latent form and remains a hurdle to eradication. CD4(+) T lymphocytes harbor the majority of the HIV reservoir, but the role of individual subsets remains unclear. CD4(+) T cells were sorted into central, transitional, effector...

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Autores principales: Venanzi Rullo, Emmanuele, Pinzone, Marilia Rita, Cannon, LaMont, Weissman, Sam, Ceccarelli, Manuela, Zurakowski, Ryan, Nunnari, Giuseppe, O’Doherty, Una
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605525/
https://www.ncbi.nlm.nih.gov/pubmed/33055422
http://dx.doi.org/10.1172/jci.insight.133157
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author Venanzi Rullo, Emmanuele
Pinzone, Marilia Rita
Cannon, LaMont
Weissman, Sam
Ceccarelli, Manuela
Zurakowski, Ryan
Nunnari, Giuseppe
O’Doherty, Una
author_facet Venanzi Rullo, Emmanuele
Pinzone, Marilia Rita
Cannon, LaMont
Weissman, Sam
Ceccarelli, Manuela
Zurakowski, Ryan
Nunnari, Giuseppe
O’Doherty, Una
author_sort Venanzi Rullo, Emmanuele
collection PubMed
description Despite the efficacy of antiretroviral therapy (ART), HIV persists in a latent form and remains a hurdle to eradication. CD4(+) T lymphocytes harbor the majority of the HIV reservoir, but the role of individual subsets remains unclear. CD4(+) T cells were sorted into central, transitional, effector memory, and naive T cells. We measured HIV DNA and performed proviral sequencing of more than 1900 proviruses in 2 subjects at 2 and 9 years after ART initiation to estimate the contribution of each subset to the reservoir. Although our study was limited to 2 subjects, we obtained comparable findings with publicly available sequences. While the HIV integration levels were lower in naive compared with memory T cells, naive cells were a major contributor to the intact proviral reservoir. Notably, proviral sequences isolated from naive cells appeared to be unique, while those retrieved from effector memory cells were mainly clonal. The number of clones increased as cells differentiated from a naive to an effector memory phenotype, suggesting naive cells repopulate the effector memory reservoir as previously shown for central memory cells. Naive T cells contribute substantially to the intact HIV reservoir and represent a significant hurdle for HIV eradication.
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spelling pubmed-76055252020-11-04 Persistence of an intact HIV reservoir in phenotypically naive T cells Venanzi Rullo, Emmanuele Pinzone, Marilia Rita Cannon, LaMont Weissman, Sam Ceccarelli, Manuela Zurakowski, Ryan Nunnari, Giuseppe O’Doherty, Una JCI Insight Research Article Despite the efficacy of antiretroviral therapy (ART), HIV persists in a latent form and remains a hurdle to eradication. CD4(+) T lymphocytes harbor the majority of the HIV reservoir, but the role of individual subsets remains unclear. CD4(+) T cells were sorted into central, transitional, effector memory, and naive T cells. We measured HIV DNA and performed proviral sequencing of more than 1900 proviruses in 2 subjects at 2 and 9 years after ART initiation to estimate the contribution of each subset to the reservoir. Although our study was limited to 2 subjects, we obtained comparable findings with publicly available sequences. While the HIV integration levels were lower in naive compared with memory T cells, naive cells were a major contributor to the intact proviral reservoir. Notably, proviral sequences isolated from naive cells appeared to be unique, while those retrieved from effector memory cells were mainly clonal. The number of clones increased as cells differentiated from a naive to an effector memory phenotype, suggesting naive cells repopulate the effector memory reservoir as previously shown for central memory cells. Naive T cells contribute substantially to the intact HIV reservoir and represent a significant hurdle for HIV eradication. American Society for Clinical Investigation 2020-10-15 /pmc/articles/PMC7605525/ /pubmed/33055422 http://dx.doi.org/10.1172/jci.insight.133157 Text en © 2020 Rullo et al. http://creativecommons.org/licenses/by/4.0/ This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Article
Venanzi Rullo, Emmanuele
Pinzone, Marilia Rita
Cannon, LaMont
Weissman, Sam
Ceccarelli, Manuela
Zurakowski, Ryan
Nunnari, Giuseppe
O’Doherty, Una
Persistence of an intact HIV reservoir in phenotypically naive T cells
title Persistence of an intact HIV reservoir in phenotypically naive T cells
title_full Persistence of an intact HIV reservoir in phenotypically naive T cells
title_fullStr Persistence of an intact HIV reservoir in phenotypically naive T cells
title_full_unstemmed Persistence of an intact HIV reservoir in phenotypically naive T cells
title_short Persistence of an intact HIV reservoir in phenotypically naive T cells
title_sort persistence of an intact hiv reservoir in phenotypically naive t cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605525/
https://www.ncbi.nlm.nih.gov/pubmed/33055422
http://dx.doi.org/10.1172/jci.insight.133157
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