Hypoxic microenvironment shapes HIV-1 replication and latency.
Basic Helix-Loop-Helix Transcription Factors
/ metabolism
Cellular Microenvironment
Flow Cytometry
HIV-1
/ physiology
Humans
Hypoxia
/ metabolism
Lymphoid Tissue
/ metabolism
Oxygen
Promoter Regions, Genetic
Real-Time Polymerase Chain Reaction
Viral Transcription
/ physiology
Virus Activation
Virus Latency
/ physiology
Virus Replication
/ physiology
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
14 07 2020
14 07 2020
Historique:
received:
27
10
2019
accepted:
17
06
2020
entrez:
16
7
2020
pubmed:
16
7
2020
medline:
22
6
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32665623
doi: 10.1038/s42003-020-1103-1
pii: 10.1038/s42003-020-1103-1
pmc: PMC7360605
doi:
Substances chimiques
Basic Helix-Loop-Helix Transcription Factors
0
endothelial PAS domain-containing protein 1
1B37H0967P
Oxygen
S88TT14065
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
376Subventions
Organisme : Medical Research Council
ID : MR/R022011/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 200838/Z/16/Z
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : 114266
Pays : United States
Organisme : Medical Research Council
ID : G0801976
Pays : United Kingdom
Organisme : Department of Health
ID : NIHR-RP-2016-06-004
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0400802
Pays : United Kingdom
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