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Hypoxic microenvironment shapes HIV-1 replication and latency

Viral replication is defined by the cellular microenvironment and one key factor is local oxygen tension, where hypoxia inducible factors (HIFs) regulate the cellular response to oxygen. Human immunodeficiency virus (HIV) infected cells within secondary lymphoid tissues exist in a low-oxygen or hypo...

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Autores principales: Zhuang, Xiaodong, Pedroza-Pacheco, Isabela, Nawroth, Isabel, Kliszczak, Anna E., Magri, Andrea, Paes, Wayne, Rubio, Claudia Orbegozo, Yang, Hongbing, Ashcroft, Margaret, Mole, David, Balfe, Peter, Borrow, Persephone, McKeating, Jane A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360605/
https://www.ncbi.nlm.nih.gov/pubmed/32665623
http://dx.doi.org/10.1038/s42003-020-1103-1
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author Zhuang, Xiaodong
Pedroza-Pacheco, Isabela
Nawroth, Isabel
Kliszczak, Anna E.
Magri, Andrea
Paes, Wayne
Rubio, Claudia Orbegozo
Yang, Hongbing
Ashcroft, Margaret
Mole, David
Balfe, Peter
Borrow, Persephone
McKeating, Jane A.
author_facet Zhuang, Xiaodong
Pedroza-Pacheco, Isabela
Nawroth, Isabel
Kliszczak, Anna E.
Magri, Andrea
Paes, Wayne
Rubio, Claudia Orbegozo
Yang, Hongbing
Ashcroft, Margaret
Mole, David
Balfe, Peter
Borrow, Persephone
McKeating, Jane A.
author_sort Zhuang, Xiaodong
collection PubMed
description Viral replication is defined by the cellular microenvironment and one key factor is local oxygen tension, where hypoxia inducible factors (HIFs) regulate the cellular response to oxygen. Human immunodeficiency virus (HIV) infected cells within secondary lymphoid tissues exist in a low-oxygen or hypoxic environment in vivo. However, the majority of studies on HIV replication and latency are performed under laboratory conditions where HIFs are inactive. We show a role for HIF-2α in restricting HIV transcription via direct binding to the viral promoter. Hypoxia reduced tumor necrosis factor or histone deacetylase inhibitor, Romidepsin, mediated reactivation of HIV and inhibiting HIF signaling-pathways reversed this phenotype. Our data support a model where the low-oxygen environment of the lymph node may suppress HIV replication and promote latency. We identify a mechanism that may contribute to the limited efficacy of latency reversing agents in reactivating HIV and suggest new strategies to control latent HIV-1.
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spelling pubmed-73606052020-07-20 Hypoxic microenvironment shapes HIV-1 replication and latency Zhuang, Xiaodong Pedroza-Pacheco, Isabela Nawroth, Isabel Kliszczak, Anna E. Magri, Andrea Paes, Wayne Rubio, Claudia Orbegozo Yang, Hongbing Ashcroft, Margaret Mole, David Balfe, Peter Borrow, Persephone McKeating, Jane A. Commun Biol Article Viral replication is defined by the cellular microenvironment and one key factor is local oxygen tension, where hypoxia inducible factors (HIFs) regulate the cellular response to oxygen. Human immunodeficiency virus (HIV) infected cells within secondary lymphoid tissues exist in a low-oxygen or hypoxic environment in vivo. However, the majority of studies on HIV replication and latency are performed under laboratory conditions where HIFs are inactive. We show a role for HIF-2α in restricting HIV transcription via direct binding to the viral promoter. Hypoxia reduced tumor necrosis factor or histone deacetylase inhibitor, Romidepsin, mediated reactivation of HIV and inhibiting HIF signaling-pathways reversed this phenotype. Our data support a model where the low-oxygen environment of the lymph node may suppress HIV replication and promote latency. We identify a mechanism that may contribute to the limited efficacy of latency reversing agents in reactivating HIV and suggest new strategies to control latent HIV-1. Nature Publishing Group UK 2020-07-14 /pmc/articles/PMC7360605/ /pubmed/32665623 http://dx.doi.org/10.1038/s42003-020-1103-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhuang, Xiaodong
Pedroza-Pacheco, Isabela
Nawroth, Isabel
Kliszczak, Anna E.
Magri, Andrea
Paes, Wayne
Rubio, Claudia Orbegozo
Yang, Hongbing
Ashcroft, Margaret
Mole, David
Balfe, Peter
Borrow, Persephone
McKeating, Jane A.
Hypoxic microenvironment shapes HIV-1 replication and latency
title Hypoxic microenvironment shapes HIV-1 replication and latency
title_full Hypoxic microenvironment shapes HIV-1 replication and latency
title_fullStr Hypoxic microenvironment shapes HIV-1 replication and latency
title_full_unstemmed Hypoxic microenvironment shapes HIV-1 replication and latency
title_short Hypoxic microenvironment shapes HIV-1 replication and latency
title_sort hypoxic microenvironment shapes hiv-1 replication and latency
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360605/
https://www.ncbi.nlm.nih.gov/pubmed/32665623
http://dx.doi.org/10.1038/s42003-020-1103-1
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