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dc.contributor.authorElder, Elizabethen
dc.contributor.authorKrishna, Benjamin Aen
dc.contributor.authorWilliamson, Jamesen
dc.contributor.authorLim, Eleanor Yen
dc.contributor.authorPoole, Emmaen
dc.contributor.authorSedikides, George Xen
dc.contributor.authorWills, Marken
dc.contributor.authorO'Connor, Christine Men
dc.contributor.authorLehner, Paulen
dc.contributor.authorSinclair, Johnen
dc.date.accessioned2019-11-13T00:30:07Z
dc.date.available2019-11-13T00:30:07Z
dc.date.issued2019-12-03en
dc.identifier.issn2161-2129
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/298846
dc.description.abstractHuman cytomegalovirus (HCMV) latency is an active process which remodels the latently infected cell to optimise latent carriage and reactivation. This is achieved, in part, through the expression of viral genes, including the G-protein coupled receptor US28. Here, we use an unbiased proteomic screen to assess changes in host proteins induced by US28, revealing that interferon-inducible genes are downregulated by US28. We validate that MHC Class II and two PYHIN proteins, MNDA and IFI16, are downregulated during experimental latency in primary human CD14+ monocytes. We find that IFI16 is targeted rapidly during the establishment of latency in a US28-dependent manner, but only in undifferentiated myeloid cells, a natural site of latent carriage. Finally, by overexpressing IFI16, we show that IFI16 can activate the viral major immediate early promoter and immediate 2 early gene expression during latency via NF-κB, a function which explains why downregulation of IFI16 during latency is advantageous for the virus.
dc.description.sponsorshipThis work was funded by the British Medical Research Council, Grant (Grant G0701279), the Wellcome Trust (Grant 109075/Z/15/A) and the Cambridge NIHR BRC Cell Phenotyping Hub.
dc.format.mediumElectronicen
dc.languageengen
dc.publisherAmerican Society for Microbiology
dc.rightsAll rights reserved
dc.rights.uri
dc.subjectMonocytesen
dc.subjectCell Lineen
dc.subjectMyeloid Cellsen
dc.subjectHumansen
dc.subjectCytomegalovirusen
dc.subjectCytomegalovirus Infectionsen
dc.subjectNF-kappa Ben
dc.subjectInterferonsen
dc.subjectReceptors, G-Protein-Coupleden
dc.subjectViral Proteinsen
dc.subjectProteomicsen
dc.subjectVirus Latencyen
dc.subjectVirus Activationen
dc.subjectCell Differentiationen
dc.subjectGene Expressionen
dc.subjectDown-Regulationen
dc.subjectGene Expression Regulation, Viralen
dc.subjectPromoter Regions, Geneticen
dc.subjectHEK293 Cellsen
dc.subjectTHP-1 Cellsen
dc.titleInterferon-Responsive Genes Are Targeted during the Establishment of Human Cytomegalovirus Latency.en
dc.typeArticle
prism.issueIdentifier6en
prism.publicationDate2019en
prism.publicationNamemBioen
prism.volume10en
dc.identifier.doi10.17863/CAM.45901
dcterms.dateAccepted2019-10-30en
rioxxterms.versionofrecord10.1128/mbio.02574-19en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-12-03en
dc.contributor.orcidElder, Elizabeth [0000-0003-1615-2642]
dc.contributor.orcidWilliamson, James [0000-0002-2009-189X]
dc.contributor.orcidWills, Mark [0000-0001-8548-5729]
dc.contributor.orcidO'Connor, Christine M [0000-0003-4943-3774]
dc.contributor.orcidLehner, Paul [0000-0001-9383-1054]
dc.identifier.eissn2150-7511
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MR/K021087/1)
pubs.funder-project-idMRC (MR/S00081X/1)
pubs.funder-project-idMRC (G0701279)
pubs.funder-project-idWELLCOME TRUST (109075/Z/15/Z)
rioxxterms.freetoread.startdate2022-11-12


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