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Progressive transformation of the HIV-1 reservoir cell profile over two decades of antiviral therapy

HIV-1 establishes a life-long reservoir of virally infected cells which cannot be eliminated by antiretroviral therapy (ART). Here, we demonstrate a markedly altered viral reservoir profile of long-term ART-treated individuals, characterized by large clones of intact proviruses preferentially integr...

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Autores principales: Lian, Xiaodong, Seiger, Kyra W., Parsons, Elizabeth M., Gao, Ce, Sun, Weiwei, Gladkov, Gregory T., Roseto, Isabelle C., Einkauf, Kevin B., Osborn, Matthew R., Chevalier, Joshua M., Jiang, Chenyang, Blackmer, Jane, Carrington, Mary, Rosenberg, Eric S., Lederman, Michael M., McMahon, Deborah K., Bosch, Ronald J., Jacobson, Jeffrey M., Gandhi, Rajesh T., Peluso, Michael J., Chun, Tae-Wook, Deeks, Steven G., Yu, Xu G., Lichterfeld, Mathias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839361/
https://www.ncbi.nlm.nih.gov/pubmed/36596305
http://dx.doi.org/10.1016/j.chom.2022.12.002
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author Lian, Xiaodong
Seiger, Kyra W.
Parsons, Elizabeth M.
Gao, Ce
Sun, Weiwei
Gladkov, Gregory T.
Roseto, Isabelle C.
Einkauf, Kevin B.
Osborn, Matthew R.
Chevalier, Joshua M.
Jiang, Chenyang
Blackmer, Jane
Carrington, Mary
Rosenberg, Eric S.
Lederman, Michael M.
McMahon, Deborah K.
Bosch, Ronald J.
Jacobson, Jeffrey M.
Gandhi, Rajesh T.
Peluso, Michael J.
Chun, Tae-Wook
Deeks, Steven G.
Yu, Xu G.
Lichterfeld, Mathias
author_facet Lian, Xiaodong
Seiger, Kyra W.
Parsons, Elizabeth M.
Gao, Ce
Sun, Weiwei
Gladkov, Gregory T.
Roseto, Isabelle C.
Einkauf, Kevin B.
Osborn, Matthew R.
Chevalier, Joshua M.
Jiang, Chenyang
Blackmer, Jane
Carrington, Mary
Rosenberg, Eric S.
Lederman, Michael M.
McMahon, Deborah K.
Bosch, Ronald J.
Jacobson, Jeffrey M.
Gandhi, Rajesh T.
Peluso, Michael J.
Chun, Tae-Wook
Deeks, Steven G.
Yu, Xu G.
Lichterfeld, Mathias
author_sort Lian, Xiaodong
collection PubMed
description HIV-1 establishes a life-long reservoir of virally infected cells which cannot be eliminated by antiretroviral therapy (ART). Here, we demonstrate a markedly altered viral reservoir profile of long-term ART-treated individuals, characterized by large clones of intact proviruses preferentially integrated in heterochromatin locations, most prominently in centromeric satellite/micro-satellite DNA. Longitudinal evaluations suggested that this specific reservoir configuration results from selection processes that promote the persistence of intact proviruses in repressive chromatin positions, while proviruses in permissive chromosomal locations are more likely to be eliminated. A bias toward chromosomal integration sites in heterochromatin locations was also observed for intact proviruses in study participants who maintained viral control after discontinuation of antiretroviral therapy. Together, these results raise the possibility that antiviral selection mechanisms during long-term ART may induce an HIV-1 reservoir structure with features of deep latency and, possibly, more limited abilities to drive rebound viremia upon treatment interruptions.
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spelling pubmed-98393612023-01-18 Progressive transformation of the HIV-1 reservoir cell profile over two decades of antiviral therapy Lian, Xiaodong Seiger, Kyra W. Parsons, Elizabeth M. Gao, Ce Sun, Weiwei Gladkov, Gregory T. Roseto, Isabelle C. Einkauf, Kevin B. Osborn, Matthew R. Chevalier, Joshua M. Jiang, Chenyang Blackmer, Jane Carrington, Mary Rosenberg, Eric S. Lederman, Michael M. McMahon, Deborah K. Bosch, Ronald J. Jacobson, Jeffrey M. Gandhi, Rajesh T. Peluso, Michael J. Chun, Tae-Wook Deeks, Steven G. Yu, Xu G. Lichterfeld, Mathias Cell Host Microbe Article HIV-1 establishes a life-long reservoir of virally infected cells which cannot be eliminated by antiretroviral therapy (ART). Here, we demonstrate a markedly altered viral reservoir profile of long-term ART-treated individuals, characterized by large clones of intact proviruses preferentially integrated in heterochromatin locations, most prominently in centromeric satellite/micro-satellite DNA. Longitudinal evaluations suggested that this specific reservoir configuration results from selection processes that promote the persistence of intact proviruses in repressive chromatin positions, while proviruses in permissive chromosomal locations are more likely to be eliminated. A bias toward chromosomal integration sites in heterochromatin locations was also observed for intact proviruses in study participants who maintained viral control after discontinuation of antiretroviral therapy. Together, these results raise the possibility that antiviral selection mechanisms during long-term ART may induce an HIV-1 reservoir structure with features of deep latency and, possibly, more limited abilities to drive rebound viremia upon treatment interruptions. Cell Press 2023-01-11 /pmc/articles/PMC9839361/ /pubmed/36596305 http://dx.doi.org/10.1016/j.chom.2022.12.002 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lian, Xiaodong
Seiger, Kyra W.
Parsons, Elizabeth M.
Gao, Ce
Sun, Weiwei
Gladkov, Gregory T.
Roseto, Isabelle C.
Einkauf, Kevin B.
Osborn, Matthew R.
Chevalier, Joshua M.
Jiang, Chenyang
Blackmer, Jane
Carrington, Mary
Rosenberg, Eric S.
Lederman, Michael M.
McMahon, Deborah K.
Bosch, Ronald J.
Jacobson, Jeffrey M.
Gandhi, Rajesh T.
Peluso, Michael J.
Chun, Tae-Wook
Deeks, Steven G.
Yu, Xu G.
Lichterfeld, Mathias
Progressive transformation of the HIV-1 reservoir cell profile over two decades of antiviral therapy
title Progressive transformation of the HIV-1 reservoir cell profile over two decades of antiviral therapy
title_full Progressive transformation of the HIV-1 reservoir cell profile over two decades of antiviral therapy
title_fullStr Progressive transformation of the HIV-1 reservoir cell profile over two decades of antiviral therapy
title_full_unstemmed Progressive transformation of the HIV-1 reservoir cell profile over two decades of antiviral therapy
title_short Progressive transformation of the HIV-1 reservoir cell profile over two decades of antiviral therapy
title_sort progressive transformation of the hiv-1 reservoir cell profile over two decades of antiviral therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839361/
https://www.ncbi.nlm.nih.gov/pubmed/36596305
http://dx.doi.org/10.1016/j.chom.2022.12.002
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