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Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses

HIV-1-infected cells that persist despite antiretroviral therapy (ART) are frequently considered “transcriptionally silent,” but active viral gene expression may occur in some cells, challenging the concept of viral latency. Applying an assay for profiling the transcriptional activity and the chromo...

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Autores principales: Einkauf, Kevin B., Osborn, Matthew R., Gao, Ce, Sun, Weiwei, Sun, Xiaoming, Lian, Xiaodong, Parsons, Elizabeth M., Gladkov, Gregory T., Seiger, Kyra W., Blackmer, Jane E., Jiang, Chenyang, Yukl, Steven A., Rosenberg, Eric S., Yu, Xu G., Lichterfeld, Mathias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8809251/
https://www.ncbi.nlm.nih.gov/pubmed/35026153
http://dx.doi.org/10.1016/j.cell.2021.12.011
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author Einkauf, Kevin B.
Osborn, Matthew R.
Gao, Ce
Sun, Weiwei
Sun, Xiaoming
Lian, Xiaodong
Parsons, Elizabeth M.
Gladkov, Gregory T.
Seiger, Kyra W.
Blackmer, Jane E.
Jiang, Chenyang
Yukl, Steven A.
Rosenberg, Eric S.
Yu, Xu G.
Lichterfeld, Mathias
author_facet Einkauf, Kevin B.
Osborn, Matthew R.
Gao, Ce
Sun, Weiwei
Sun, Xiaoming
Lian, Xiaodong
Parsons, Elizabeth M.
Gladkov, Gregory T.
Seiger, Kyra W.
Blackmer, Jane E.
Jiang, Chenyang
Yukl, Steven A.
Rosenberg, Eric S.
Yu, Xu G.
Lichterfeld, Mathias
author_sort Einkauf, Kevin B.
collection PubMed
description HIV-1-infected cells that persist despite antiretroviral therapy (ART) are frequently considered “transcriptionally silent,” but active viral gene expression may occur in some cells, challenging the concept of viral latency. Applying an assay for profiling the transcriptional activity and the chromosomal locations of individual proviruses, we describe a global genomic and epigenetic map of transcriptionally active and silent proviral species and evaluate their longitudinal evolution in persons receiving suppressive ART. Using genome-wide epigenetic reference data, we show that proviral transcriptional activity is associated with activating epigenetic chromatin features in linear proximity of integration sites and in their inter- and intrachromosomal contact regions. Transcriptionally active proviruses were actively selected against during prolonged ART; however, this pattern was violated by large clones of virally infected cells that may outcompete negative selection forces through elevated intrinsic proliferative activity. Our results suggest that transcriptionally active proviruses are dynamically evolving under selection pressure by host factors.
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spelling pubmed-88092512022-02-07 Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses Einkauf, Kevin B. Osborn, Matthew R. Gao, Ce Sun, Weiwei Sun, Xiaoming Lian, Xiaodong Parsons, Elizabeth M. Gladkov, Gregory T. Seiger, Kyra W. Blackmer, Jane E. Jiang, Chenyang Yukl, Steven A. Rosenberg, Eric S. Yu, Xu G. Lichterfeld, Mathias Cell Article HIV-1-infected cells that persist despite antiretroviral therapy (ART) are frequently considered “transcriptionally silent,” but active viral gene expression may occur in some cells, challenging the concept of viral latency. Applying an assay for profiling the transcriptional activity and the chromosomal locations of individual proviruses, we describe a global genomic and epigenetic map of transcriptionally active and silent proviral species and evaluate their longitudinal evolution in persons receiving suppressive ART. Using genome-wide epigenetic reference data, we show that proviral transcriptional activity is associated with activating epigenetic chromatin features in linear proximity of integration sites and in their inter- and intrachromosomal contact regions. Transcriptionally active proviruses were actively selected against during prolonged ART; however, this pattern was violated by large clones of virally infected cells that may outcompete negative selection forces through elevated intrinsic proliferative activity. Our results suggest that transcriptionally active proviruses are dynamically evolving under selection pressure by host factors. Cell Press 2022-01-20 /pmc/articles/PMC8809251/ /pubmed/35026153 http://dx.doi.org/10.1016/j.cell.2021.12.011 Text en © 2021 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
Einkauf, Kevin B.
Osborn, Matthew R.
Gao, Ce
Sun, Weiwei
Sun, Xiaoming
Lian, Xiaodong
Parsons, Elizabeth M.
Gladkov, Gregory T.
Seiger, Kyra W.
Blackmer, Jane E.
Jiang, Chenyang
Yukl, Steven A.
Rosenberg, Eric S.
Yu, Xu G.
Lichterfeld, Mathias
Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses
title Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses
title_full Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses
title_fullStr Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses
title_full_unstemmed Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses
title_short Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses
title_sort parallel analysis of transcription, integration, and sequence of single hiv-1 proviruses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8809251/
https://www.ncbi.nlm.nih.gov/pubmed/35026153
http://dx.doi.org/10.1016/j.cell.2021.12.011
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