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dc.contributor.authorStevenson, Nigel
dc.contributor.authorBowie, Andrew
dc.contributor.authorRoberts, Kim
dc.contributor.authorBourke, Nollaig
dc.contributor.authorO'Farrelly, Cliona
dc.date.accessioned2019-08-13T14:47:05Z
dc.date.available2019-08-13T14:47:05Z
dc.date.issued2017-05
dc.date.submitted2017en
dc.identifier.citationMahony R, Gargan S, Roberts KL, Bourke N, Keating SE, Bowie AG, O'Farrelly C, Stevenson NJ. A novel anti-viral role for STAT3 in IFN-α signalling responses, Cellular and Molecular Life Sciences, 74, 9, 2017, 1755 - 1764en
dc.identifier.otherY
dc.identifier.urihttp://hdl.handle.net/2262/89184
dc.descriptionPUBLISHEDen
dc.description.abstractThe cytokine, Interferon (IFN)-α, induces a wide spectrum of anti-viral mediators, via the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. STAT1 and STAT2 are well characterised to upregulate IFN-stimulated gene (ISG) expression; but even though STAT3 is also activated by IFN-α, its role in anti-viral ISG induction is unclear. Several viruses, including Hepatitis C and Mumps, reduce cellular STAT3 protein levels, via the promotion of ubiquitin-mediated proteasomal degradation. This viral immune evasion mechanism suggests an undiscovered anti-viral role for STAT3 in IFN-α signalling. To investigate STAT3’s functional involvement in this Type I IFN pathway, we first analysed its effect upon the replication of two viruses, Influenza and Vaccinia. Viral plaque assays, using Wild Type (WT) andSTAT3-/- Murine Embryonic Fibroblasts (MEFs), revealed that STAT3 is required for the inhibition of Influenza and Vaccinia replication. Furthermore, STAT3 shRNA knockdown also enhanced Influenza replication and hindered induction of several, well characterised, anti-viral ISGs: PKR, OAS2, MxB and ISG15; while STAT3 expression had no effect upon induction of a separate ISG group: Viperin, IFI27, CXCL10 and CCL5. These discoveries reveal, for the first time, an anti-viral role forSTAT3 in the IFN-a pathway and characterise a requirement for STAT3 in the expression of specific ISGs. These findings also identify STAT3 as a therapeutic target against viral infection and highlight it as an essential pathway component for endogenous and therapeutic IFN-a responsiveness.en
dc.format.extent1755en
dc.format.extent1764en
dc.language.isoenen
dc.publisherSpringeren
dc.relation.ispartofseriesCellular and Molecular Life Sciences;
dc.relation.ispartofseries74;
dc.relation.ispartofseries9;
dc.rightsYen
dc.subjectJanus kinase/signal transducer of activator of transcription(JAK/STAT)en
dc.subjectSTAT3en
dc.subjectIFN-stimulated gene (ISG)en
dc.subjectVaccinia virusen
dc.subjectInfluenza virusen
dc.subjectAnti-viralen
dc.subjectInterferon-alpha (IFN-α)en
dc.titleA novel anti-viral role for STAT3 in IFN-α signalling responses.en
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/kroberts
dc.identifier.peoplefinderurlhttp://people.tcd.ie/ofarrecl
dc.identifier.peoplefinderurlhttp://people.tcd.ie/agbowie
dc.identifier.peoplefinderurlhttp://people.tcd.ie/nbourke
dc.identifier.peoplefinderurlhttp://people.tcd.ie/stevennj
dc.identifier.rssinternalid167558
dc.identifier.doihttps://doi.org/10.1007/s00018-016-2435-3
dc.rights.ecaccessrightsembargoedAccess
dc.date.ecembargoEndDate2067-05-01
dc.subject.TCDThemeImmunology, Inflammation & Infectionen
dc.status.accessibleNen


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