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Integration in oncogenes plays only a minor role in determining the in vivo distribution of HIV integration sites before or during suppressive antiretroviral therapy

HIV persists during antiretroviral therapy (ART) as integrated proviruses in cells descended from a small fraction of the CD4+ T cells infected prior to the initiation of ART. To better understand what controls HIV persistence and the distribution of integration sites (IS), we compared about 15,000...

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Autores principales: Coffin, John M., Bale, Michael J., Wells, Daria, Guo, Shuang, Luke, Brian, Zerbato, Jennifer M., Sobolewski, Michele D., Sia, Twan, Shao, Wei, Wu, Xiaolin, Maldarelli, Frank, Kearney, Mary F., Mellors, John W., Hughes, Stephen H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055010/
https://www.ncbi.nlm.nih.gov/pubmed/33826675
http://dx.doi.org/10.1371/journal.ppat.1009141
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author Coffin, John M.
Bale, Michael J.
Wells, Daria
Guo, Shuang
Luke, Brian
Zerbato, Jennifer M.
Sobolewski, Michele D.
Sia, Twan
Shao, Wei
Wu, Xiaolin
Maldarelli, Frank
Kearney, Mary F.
Mellors, John W.
Hughes, Stephen H.
author_facet Coffin, John M.
Bale, Michael J.
Wells, Daria
Guo, Shuang
Luke, Brian
Zerbato, Jennifer M.
Sobolewski, Michele D.
Sia, Twan
Shao, Wei
Wu, Xiaolin
Maldarelli, Frank
Kearney, Mary F.
Mellors, John W.
Hughes, Stephen H.
author_sort Coffin, John M.
collection PubMed
description HIV persists during antiretroviral therapy (ART) as integrated proviruses in cells descended from a small fraction of the CD4+ T cells infected prior to the initiation of ART. To better understand what controls HIV persistence and the distribution of integration sites (IS), we compared about 15,000 and 54,000 IS from individuals pre-ART and on ART, respectively, with approximately 395,000 IS from PBMC infected in vitro. The distribution of IS in vivo is quite similar to the distribution in PBMC, but modified by selection against proviruses in expressed genes, by selection for proviruses integrated into one of 7 specific genes, and by clonal expansion. Clones in which a provirus integrated in an oncogene contributed to cell survival comprised only a small fraction of the clones persisting in on ART. Mechanisms that do not involve the provirus, or its location in the host genome, are more important in determining which clones expand and persist.
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spelling pubmed-80550102021-04-30 Integration in oncogenes plays only a minor role in determining the in vivo distribution of HIV integration sites before or during suppressive antiretroviral therapy Coffin, John M. Bale, Michael J. Wells, Daria Guo, Shuang Luke, Brian Zerbato, Jennifer M. Sobolewski, Michele D. Sia, Twan Shao, Wei Wu, Xiaolin Maldarelli, Frank Kearney, Mary F. Mellors, John W. Hughes, Stephen H. PLoS Pathog Research Article HIV persists during antiretroviral therapy (ART) as integrated proviruses in cells descended from a small fraction of the CD4+ T cells infected prior to the initiation of ART. To better understand what controls HIV persistence and the distribution of integration sites (IS), we compared about 15,000 and 54,000 IS from individuals pre-ART and on ART, respectively, with approximately 395,000 IS from PBMC infected in vitro. The distribution of IS in vivo is quite similar to the distribution in PBMC, but modified by selection against proviruses in expressed genes, by selection for proviruses integrated into one of 7 specific genes, and by clonal expansion. Clones in which a provirus integrated in an oncogene contributed to cell survival comprised only a small fraction of the clones persisting in on ART. Mechanisms that do not involve the provirus, or its location in the host genome, are more important in determining which clones expand and persist. Public Library of Science 2021-04-07 /pmc/articles/PMC8055010/ /pubmed/33826675 http://dx.doi.org/10.1371/journal.ppat.1009141 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Coffin, John M.
Bale, Michael J.
Wells, Daria
Guo, Shuang
Luke, Brian
Zerbato, Jennifer M.
Sobolewski, Michele D.
Sia, Twan
Shao, Wei
Wu, Xiaolin
Maldarelli, Frank
Kearney, Mary F.
Mellors, John W.
Hughes, Stephen H.
Integration in oncogenes plays only a minor role in determining the in vivo distribution of HIV integration sites before or during suppressive antiretroviral therapy
title Integration in oncogenes plays only a minor role in determining the in vivo distribution of HIV integration sites before or during suppressive antiretroviral therapy
title_full Integration in oncogenes plays only a minor role in determining the in vivo distribution of HIV integration sites before or during suppressive antiretroviral therapy
title_fullStr Integration in oncogenes plays only a minor role in determining the in vivo distribution of HIV integration sites before or during suppressive antiretroviral therapy
title_full_unstemmed Integration in oncogenes plays only a minor role in determining the in vivo distribution of HIV integration sites before or during suppressive antiretroviral therapy
title_short Integration in oncogenes plays only a minor role in determining the in vivo distribution of HIV integration sites before or during suppressive antiretroviral therapy
title_sort integration in oncogenes plays only a minor role in determining the in vivo distribution of hiv integration sites before or during suppressive antiretroviral therapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055010/
https://www.ncbi.nlm.nih.gov/pubmed/33826675
http://dx.doi.org/10.1371/journal.ppat.1009141
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