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dc.contributor.authorLau, Bettyen
dc.contributor.authorPoole, Emmaen
dc.contributor.authorVan, Damme Ellenen
dc.contributor.authorBunkens, Lieveen
dc.contributor.authorSowash, Madeleineen
dc.contributor.authorKing, Harryen
dc.contributor.authorMurphy, Eainen
dc.contributor.authorWills, Marken
dc.contributor.authorVan, Loock Marnixen
dc.contributor.authorSinclair, Johnen
dc.date.accessioned2016-08-19T07:02:14Z
dc.date.available2016-08-19T07:02:14Z
dc.date.issued2016-07-13en
dc.identifier.issn0022-1317
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/257348
dc.description.abstractHuman cytomegalovirus (HCMV), a member of the herpesvirus family, can cause significant morbidity and mortality in immune compromised patients resulting from either primary lytic infection or reactivation from latency. Latent infection is associated with a restricted viral transcription programme compared to lytic infection which consists of defined protein coding RNAs but also includes a number of virally encoded microRNAs (miRNAs). One of these, miR-UL112-1, is known to target the major lytic IE72 transcript but, to date, a functional role for miR-UL112-1 during latent infection has not been shown. To address this, we have analysed latent infection in myeloid cells using a virus in which the target site for miR-UL112-1 in the 3' untranslated region of IE72 was removed such that any IE72 RNA present during latent infection would no longer be subject to regulation by miR-UL112-1 through the RNAi pathway. Our data show that removal of the miR- UL112-1 target site in IE72 results in increased levels of IE72 RNA in experimentally latent primary monocytes. Furthermore, this resulted in induction of IE expression detectable by IE-specific cytotoxic T cells (CTLs); no such CTL recognition of monocytes latently infected with wild-type virus was observed. We also recapitulated these findings in the more tractable THP-1 cell line model of latency. These observations argue that an important role for miR-UL112-1 during latency is to ensure tight control of lytic viral IE gene expression thereby preventing recognition of latently infected cells by the host's potent pre-existing anti-viral CTL response.
dc.description.sponsorshipMedical Research Council (Grant ID: G:0701279); National Institute for Health Research Biomedical Research Centre
dc.languageEnglishen
dc.language.isoenen
dc.publisherMicrobiology Society
dc.titleHuman cytomegalovirus miR-UL112-1 promotes the down-regulation of viral immediate early gene expression during latency to prevent T cell recognition of latently infected cellsen
dc.typeArticle
dc.description.versionThis is the author accepted manuscript. The final version is available from the Microbiology Society via http://dx.doi.org/10.1099/jgv.0.000546en
prism.publicationDate2016en
prism.publicationNameJournal of General Virologyen
dc.identifier.doi10.17863/CAM.1282
dcterms.dateAccepted2016-07-11en
rioxxterms.versionofrecord10.1099/jgv.0.000546en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2016-07-13en
dc.contributor.orcidPoole, Emma [0000-0003-3904-6121]
dc.contributor.orcidWills, Mark [0000-0001-8548-5729]
dc.contributor.orcidSinclair, John [0000-0002-2616-9571]
dc.identifier.eissn1465-2099
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MR/K021087/1)
pubs.funder-project-idMRC (G0701279)
rioxxterms.freetoread.startdate2017-07-13


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