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dc.contributor.authorMankouri, J
dc.contributor.authorFragkoudis, R
dc.contributor.authorRichards, K
dc.contributor.authorWetherill, L
dc.contributor.authorHarris, M
dc.contributor.authorKohl, A
dc.contributor.authorElliott, Richard Michael
dc.contributor.authorMacDonald, A
dc.date.accessioned2010-11-01T14:30:03Z
dc.date.available2010-11-01T14:30:03Z
dc.date.issued2010-02
dc.identifier.citationMankouri , J , Fragkoudis , R , Richards , K , Wetherill , L , Harris , M , Kohl , A , Elliott , R M & MacDonald , A 2010 , ' Optineurin negatively regulates the induction of IFNβ in response to RNA virus infection ' PLoS Pathogens , vol. 6 , no. 2 , e1000778 . https://doi.org/10.1371/journal.ppat.1000778en
dc.identifier.issn1553-7366
dc.identifier.otherPURE: 3939387
dc.identifier.otherPURE UUID: 3b7b00ba-9a56-4420-9e40-7234f804bfdf
dc.identifier.otherScopus: 77649269693
dc.identifier.urihttp://hdl.handle.net/10023/1191
dc.descriptionWork in RME laboratories is funded by the Wellcome Trust [079810/Z/06/Z].en
dc.description.abstractThe innate immune response provides a critical defense against microbial infections, including viruses. These are recognised by pattern recognition receptors including Toll-like receptors (TLRs) and RIG-I like helicases (RLHs). Detection of virus triggers signalling cascades that induce transcription of type I interferons including IFNb, which are pivotal for the initiation of an anti-viral state. Despite the essential role of IFNb in the anti-viral response, there is an incomplete understanding of the negative regulation of IFNb induction. Here we provide evidence that expression of the Nemo-related protein, optineurin (NRP/FIP2), has a role in the inhibition of virus-triggered IFNb induction. Over-expression of optineurin inhibited Sendaivirus (SeV) and dsRNA triggered induction of IFNb, whereas depletion of optineurin with siRNA promoted virus-induced IFNb production and decreased RNA virus replication. Immunoprecipitation and immunofluorescence studies identified optineurin in a protein complex containing the antiviral protein kinase TBK1 and the ubiquitin ligase TRAF3. Furthermore, mutagenesis studies determined that binding of ubiquitin was essential for both the correct sub-cellular localisation and the inhibitory function of optineurin. This work identifies optineurin as a critical regulator of antiviral signalling and potential target for future antiviral therapy.
dc.format.extent13
dc.language.isoeng
dc.relation.ispartofPLoS Pathogensen
dc.rights(c) 2010 Mankouri et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectQR355 Virologyen
dc.subject.lccQR355en
dc.titleOptineurin negatively regulates the induction of IFNβ in response to RNA virus infectionen
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/10.1371/journal.ppat.1000778
dc.description.statusPeer revieweden
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=77649269693&partnerID=8YFLogxKen


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