Show simple item record

dc.contributor.authorLau, Betty
dc.contributor.authorPoole, Emma
dc.contributor.authorVan Damme, Ellen
dc.contributor.authorBunkens, Lieve
dc.contributor.authorSowash, Madeleine
dc.contributor.authorKing, Harry
dc.contributor.authorMurphy, Eain
dc.contributor.authorWills, Mark
dc.contributor.authorVan Loock, Marnix
dc.contributor.authorSinclair, John
dc.date.accessioned2016-08-19T07:02:14Z
dc.date.available2016-08-19T07:02:14Z
dc.date.issued2016-09
dc.identifier.issn0022-1317
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/257348
dc.description.abstractHuman cytomegalovirus, 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' UTR 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 immediate early (IE) gene expression that is 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 immediate early (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.languageEnglish
dc.language.isoen
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 cells.
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.0.000546
prism.publicationDate2016
prism.publicationNameJ Gen Virol
dc.identifier.doi10.17863/CAM.1282
dcterms.dateAccepted2016-07-11
rioxxterms.versionofrecord10.1099/jgv.0.000546
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2016-07-13
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/Review
pubs.funder-project-idMedical Research Council (MR/K021087/1)
pubs.funder-project-idMedical Research Council (G0701279)
cam.issuedOnline2016-07-13
rioxxterms.freetoread.startdate2017-07-13


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record