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dc.contributor.authorLyon, Shelby M.
dc.contributor.authorYetming, Kristen D.
dc.contributor.authorPaulus, Christina
dc.contributor.authorNevels, Michael
dc.contributor.authorKalejta, Robert F.
dc.contributor.editorSchultz-cherry, Stacey
dc.date.accessioned2020-10-15T14:30:10Z
dc.date.available2020-10-15T14:30:10Z
dc.date.issued2020-09
dc.identifier.citationLyon , S M , Yetming , K D , Paulus , C , Nevels , M , Kalejta , R F & Schultz-cherry , S (ed.) 2020 , ' Human cytomegalovirus genomes survive mitosis via the IE19 chromatin-tethering domain ' , mBio , vol. 11 , no. 5 , e02410-20 . https://doi.org/10.1128/mBio.02410-20en
dc.identifier.issn2150-7511
dc.identifier.otherPURE: 270731730
dc.identifier.otherPURE UUID: 2191ce7a-a965-415f-b9f0-3a5ab7789de8
dc.identifier.othercrossref: 10.1128/mBio.02410-20
dc.identifier.otherScopus: 85091771339
dc.identifier.otherORCID: /0000-0002-7115-407X/work/82179663
dc.identifier.otherORCID: /0000-0002-4123-5629/work/82179676
dc.identifier.otherWOS: 000579503600078
dc.identifier.urihttp://hdl.handle.net/10023/20787
dc.descriptionThis work was supported by NIH grants AI139180 and AI130089 to R.F.K. S.M.L. was supported by NRSA award T32 CA009135.en
dc.description.abstractThe genomes of DNA tumor viruses regain nuclear localization after nuclear envelope breakdown during mitosis through the action of a viral protein with a chromatin-tethering domain (CTD). Here, we report that the human cytomegalovirus (HCMV) genome is maintained during mitosis by the CTD of the viral IE19 protein. Deletion of the IE19 CTD or disruption of the IE19 splice acceptor site reduced viral genome maintenance and progeny virion formation during infection of dividing fibroblasts, both of which were rescued by IE19 ectopic expression. The discovery of a viral genome maintenance factor during productive infection provides new insight into the mode of HCMV infection implicated in birth defects, organ transplant failure, and cancer. IMPORTANCE Human cytomegalovirus (HCMV) is the leading infectious cause of birth defects, represents a serious complication for immunocompromised HIV/AIDS and organ transplant patients, and contributes to both immunosenescence and cardiovascular diseases. HCMV is also implicated in cancers such as glioblastoma multiforme (GBM) and infects ex vivo-cultured GBM tumor cells. In dividing tumor cells, the genomes of DNA tumor viruses regain nuclear localization after nuclear envelope breakdown during mitosis. This mitotic survival is mediated by a viral protein with a chromatin-tethering domain (CTD). Here, we report that the HCMV genome is maintained in dividing fibroblasts by the CTD of the viral IE19 protein. The discovery of a viral genome maintenance factor during productive infection could help explain viral genome dynamics within HCMV-positive tumors as well as during latency.
dc.format.extent17
dc.language.isoeng
dc.relation.ispartofmBioen
dc.rightsCopyright © 2020 Lyon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.en
dc.subjectCanceren
dc.subjectChromatinen
dc.subjectHerpesen
dc.subjectLatencyen
dc.subjectMitosisen
dc.subjectTranscriptionen
dc.subjectQH426 Geneticsen
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subjectNDASen
dc.subject.lccQH426en
dc.subject.lccRC0254en
dc.titleHuman cytomegalovirus genomes survive mitosis via the IE19 chromatin-tethering domainen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1128/mBio.02410-20
dc.description.statusPeer revieweden


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