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dc.contributor.authorZhuang, Xiaodong
dc.contributor.authorPedroza-Pacheco, Isabela
dc.contributor.authorNawroth, Isabel
dc.contributor.authorKliszczak, Anna E.
dc.contributor.authorMagri, Andrea
dc.contributor.authorPaes, Wayne
dc.contributor.authorRubio, Claudia Orbegozo
dc.contributor.authorYang, Hongbing
dc.contributor.authorAshcroft, Margaret
dc.contributor.authorMole, David
dc.contributor.authorBalfe, Peter
dc.contributor.authorBorrow, Persephone
dc.contributor.authorMcKeating, Jane A.
dc.date.accessioned2021-02-18T18:36:41Z
dc.date.available2021-02-18T18:36:41Z
dc.date.issued2020-07-14
dc.date.submitted2019-10-27
dc.identifier.others42003-020-1103-1
dc.identifier.other1103
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/317854
dc.description.abstractAbstract: 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.
dc.languageen
dc.publisherNature Publishing Group UK
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectArticle
dc.subject/631/326/596/2557
dc.subject/631/250/254
dc.subject/13/1
dc.subject/96
dc.subject/82
dc.subject/64
dc.subject/38
dc.subjectarticle
dc.titleHypoxic microenvironment shapes HIV-1 replication and latency
dc.typeArticle
dc.date.updated2021-02-18T18:36:40Z
prism.issueIdentifier1
prism.publicationNameCommunications Biology
prism.volume3
dc.identifier.doi10.17863/CAM.64969
dcterms.dateAccepted2020-06-17
rioxxterms.versionofrecord10.1038/s42003-020-1103-1
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidPaes, Wayne [0000-0002-0529-2765]
dc.contributor.orcidAshcroft, Margaret [0000-0002-0066-3707]
dc.contributor.orcidBalfe, Peter [0000-0002-6246-0876]
dc.contributor.orcidBorrow, Persephone [0000-0002-3877-9780]
dc.contributor.orcidMcKeating, Jane A. [0000-0002-7229-5886]
dc.identifier.eissn2399-3642
pubs.funder-project-idRCUK | Medical Research Council (MRC) (MR/R022011/1)
pubs.funder-project-idDivision of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) (114266)
pubs.funder-project-idDH | National Institute for Health Research (NIHR) (NIHR-RP-2016-06-004)
pubs.funder-project-idEC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) (H2020-667273-HEPCAR)


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)