Hypoxic microenvironment shapes HIV-1 replication and latency
View / Open Files
Authors
Zhuang, Xiaodong
Pedroza-Pacheco, Isabela
Nawroth, Isabel
Kliszczak, Anna E.
Magri, Andrea
Rubio, Claudia Orbegozo
Yang, Hongbing
Mole, David
Publication Date
2020-07-14Journal Title
Communications Biology
Publisher
Nature Publishing Group UK
Volume
3
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Zhuang, X., Pedroza-Pacheco, I., Nawroth, I., Kliszczak, A. E., Magri, A., Paes, W., Rubio, C. O., et al. (2020). Hypoxic microenvironment shapes HIV-1 replication and latency. Communications Biology, 3 (1) https://doi.org/10.1038/s42003-020-1103-1
Abstract
Abstract: 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.
Keywords
Article, /631/326/596/2557, /631/250/254, /13/1, /96, /82, /64, /38, article
Sponsorship
RCUK | Medical Research Council (MRC) (MR/R022011/1)
Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) (114266)
DH | National Institute for Health Research (NIHR) (NIHR-RP-2016-06-004)
EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) (H2020-667273-HEPCAR)
Identifiers
s42003-020-1103-1, 1103
External DOI: https://doi.org/10.1038/s42003-020-1103-1
This record's URL: https://www.repository.cam.ac.uk/handle/1810/317854
Rights
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.