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HIV-1 Proviral Transcription and Latency in the New Era

Three decades of extensive work in the HIV field have revealed key viral and host cell factors controlling proviral transcription. Various models of transcriptional regulation have emerged based on the collective information from in vitro assays and work in both immortalized and primary cell-based m...

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Autores principales: Shukla, Ashutosh, Ramirez, Nora-Guadalupe P., D’Orso, Iván
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291205/
https://www.ncbi.nlm.nih.gov/pubmed/32443452
http://dx.doi.org/10.3390/v12050555
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author Shukla, Ashutosh
Ramirez, Nora-Guadalupe P.
D’Orso, Iván
author_facet Shukla, Ashutosh
Ramirez, Nora-Guadalupe P.
D’Orso, Iván
author_sort Shukla, Ashutosh
collection PubMed
description Three decades of extensive work in the HIV field have revealed key viral and host cell factors controlling proviral transcription. Various models of transcriptional regulation have emerged based on the collective information from in vitro assays and work in both immortalized and primary cell-based models. Here, we provide a recount of the past and current literature, highlight key regulatory aspects, and further describe potential limitations of previous studies. We particularly delve into critical steps of HIV gene expression including the role of the integration site, nucleosome positioning and epigenomics, and the transition from initiation to pausing and pause release. We also discuss open questions in the field concerning the generality of previous regulatory models to the control of HIV transcription in patients under suppressive therapy, including the role of the heterogeneous integration landscape, clonal expansion, and bottlenecks to eradicate viral persistence. Finally, we propose that building upon previous discoveries and improved or yet-to-be discovered technologies will unravel molecular mechanisms of latency establishment and reactivation in a “new era”.
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spelling pubmed-72912052020-06-17 HIV-1 Proviral Transcription and Latency in the New Era Shukla, Ashutosh Ramirez, Nora-Guadalupe P. D’Orso, Iván Viruses Review Three decades of extensive work in the HIV field have revealed key viral and host cell factors controlling proviral transcription. Various models of transcriptional regulation have emerged based on the collective information from in vitro assays and work in both immortalized and primary cell-based models. Here, we provide a recount of the past and current literature, highlight key regulatory aspects, and further describe potential limitations of previous studies. We particularly delve into critical steps of HIV gene expression including the role of the integration site, nucleosome positioning and epigenomics, and the transition from initiation to pausing and pause release. We also discuss open questions in the field concerning the generality of previous regulatory models to the control of HIV transcription in patients under suppressive therapy, including the role of the heterogeneous integration landscape, clonal expansion, and bottlenecks to eradicate viral persistence. Finally, we propose that building upon previous discoveries and improved or yet-to-be discovered technologies will unravel molecular mechanisms of latency establishment and reactivation in a “new era”. MDPI 2020-05-18 /pmc/articles/PMC7291205/ /pubmed/32443452 http://dx.doi.org/10.3390/v12050555 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Shukla, Ashutosh
Ramirez, Nora-Guadalupe P.
D’Orso, Iván
HIV-1 Proviral Transcription and Latency in the New Era
title HIV-1 Proviral Transcription and Latency in the New Era
title_full HIV-1 Proviral Transcription and Latency in the New Era
title_fullStr HIV-1 Proviral Transcription and Latency in the New Era
title_full_unstemmed HIV-1 Proviral Transcription and Latency in the New Era
title_short HIV-1 Proviral Transcription and Latency in the New Era
title_sort hiv-1 proviral transcription and latency in the new era
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291205/
https://www.ncbi.nlm.nih.gov/pubmed/32443452
http://dx.doi.org/10.3390/v12050555
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