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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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”. |
format | Online Article Text |
id | pubmed-7291205 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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