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dc.contributor.authorReitsma, Justin M
dc.contributor.authorSato, Hiromi
dc.contributor.authorNevels, Michael
dc.contributor.authorTerhune, Scott S
dc.contributor.authorPaulus, Christina
dc.date.accessioned2018-07-03T16:30:37Z
dc.date.available2018-07-03T16:30:37Z
dc.date.issued2013-10
dc.identifier.citationReitsma , J M , Sato , H , Nevels , M , Terhune , S S & Paulus , C 2013 , ' Human cytomegalovirus IE1 protein disrupts interleukin-6 signaling by sequestering STAT3 in the nucleus ' , Journal of Virology , vol. 87 , no. 19 , pp. 10763-10776 . https://doi.org/10.1128/JVI.01197-13en
dc.identifier.issn0022-538X
dc.identifier.otherPURE: 173809915
dc.identifier.otherPURE UUID: 48e8bb96-5d65-4aa3-803b-12f7589109ef
dc.identifier.otherPubMed: 23903834
dc.identifier.otherScopus: 84886016486
dc.identifier.otherORCID: /0000-0002-7115-407X/work/28624009
dc.identifier.otherORCID: /0000-0002-4123-5629/work/47136635
dc.identifier.urihttp://hdl.handle.net/10023/14872
dc.description.abstractIn the canonical STAT3 signaling pathway, binding of agonist to receptors activates Janus kinases that phosphorylate cytoplasmic STAT3 at tyrosine 705 (Y705). Phosphorylated STAT3 dimers accumulate in the nucleus and drive the expression of genes involved in inflammation, angiogenesis, invasion, and proliferation. Here, we demonstrate that human cytomegalovirus (HCMV) infection rapidly promotes nuclear localization of STAT3 in the absence of robust phosphorylation at Y705. Furthermore, infection disrupts interleukin-6 (IL-6)-induced phosphorylation of STAT3 and expression of a subset of IL-6-induced STAT3-regulated genes, including SOCS3. We show that the HCMV 72-kDa immediate-early 1 (IE1) protein associates with STAT3 and is necessary to localize STAT3 to the nucleus during infection. Furthermore, expression of IE1 is sufficient to disrupt IL-6-induced phosphorylation of STAT3, binding of STAT3 to the SOCS3 promoter, and SOCS3 gene expression. Finally, inhibition of STAT3 nuclear localization or STAT3 expression during infection is linked to diminished HCMV genome replication. Viral gene expression is also disrupted, with the greatest impact seen following viral DNA synthesis. Our study identifies IE1 as a new regulator of STAT3 intracellular localization and IL-6 signaling and points to an unanticipated role of STAT3 in HCMV infection.
dc.format.extent14
dc.language.isoeng
dc.relation.ispartofJournal of Virologyen
dc.rights© 2013, American Society for Microbiology. This work has been made available online in accordance with the publisher’s policies. This is the author created accepted version manuscript following peer review and as such may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1128/JVI.01197-13en
dc.subjectAnimalsen
dc.subjectAstrocytomaen
dc.subjectBlotting, Westernen
dc.subjectCell Nucleusen
dc.subjectCells, Cultureden
dc.subjectCytomegalovirusen
dc.subjectCytomegalovirus Infectionsen
dc.subjectFibroblastsen
dc.subjectFluorescent Antibody Techniqueen
dc.subjectHumansen
dc.subjectImmediate-Early Proteinsen
dc.subjectInterleukin-6en
dc.subjectMiceen
dc.subjectPhosphorylationen
dc.subjectRNA, Messengeren
dc.subjectReal-Time Polymerase Chain Reactionen
dc.subjectReverse Transcriptase Polymerase Chain Reactionen
dc.subjectSTAT3 Transcription Factoren
dc.subjectSignal Transductionen
dc.subjectTrans-Activatorsen
dc.subjectVirus Replicationen
dc.subjectQH301 Biologyen
dc.subjectQR355 Virologyen
dc.subject.lccQH301en
dc.subject.lccQR355en
dc.titleHuman cytomegalovirus IE1 protein disrupts interleukin-6 signaling by sequestering STAT3 in the nucleusen
dc.typeJournal articleen
dc.description.versionPostprinten
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/JVI.01197-13
dc.description.statusPeer revieweden


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