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dc.contributor.authorMatthews, K.
dc.contributor.authorPham, A.
dc.contributor.authorFrieman, M.
dc.date.accessioned2020-03-27T15:13:16Z
dc.date.available2020-03-27T15:13:16Z
dc.date.issued2014
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84938521107&doi=10.1186%2fs12985-014-0209-9&partnerID=40&md5=f07c2e5f89d8a155d9c62e2160aab0fe
dc.identifier.urihttp://hdl.handle.net/10713/12411
dc.description.abstractBackground: The outcome of a viral infection is regulated by complex interactions of viral and host factors. SARS coronavirus (SARS-CoV) engages and regulates several innate immune response pathways during infection. We have previously shown that the SARS-CoV Papain-like Protease (PLpro) inhibits type I interferon (IFN) by inhibiting IRF3 phosphorylation thereby blocking downstream Interferon induction. This finding prompted us to identify other potential mechanisms of inhibition of PLpro on IFN induction. Methods: We have used plasmids expressing PLpro and IRF3 including an IRF3 mutant that is constitutively active, called IRF3(5D). In these experiments we utilize transfections, chromatin immunoprecipitation, Electro-mobility Shift Assays (EMSA) and protein localization to identify where IRF3 and IRF3(5D) are inhibited by PLpro. Results: Here we show that PLpro also inhibits IRF3 activation at a step after phosphorylation and that this inhibition is dependent on the de-ubiquitination (DUB) activity of PLpro. We found that PLpro is able to block the type I IFN induction of a constitutively active IRF3, but does not inhibit IRF3 dimerization, nuclear localization or DNA binding. However, inhibition of PLpro's DUB activity by mutagenesis blocked the IRF3 inhibition activity of PLpro, suggesting a role for IRF3 ubiquitination in induction of a type I IFN innate immune response. Conclusion: These results demonstrate an additional mechanism that PLpro is able to inhibit IRF3 signaling. These data suggest novel innate immune antagonism activities of PLpro that may contribute to SARS-CoV pathogenesis. Copyright 2014 Matthews et al.en_US
dc.description.sponsorshipNational Institutes of Health, NIH: K22AI077797en_US
dc.description.urihttps://doi.org/10.1186/s12985-014-0209-9en_US
dc.language.isoen_USen_US
dc.publisherBioMed Central Ltd.en_US
dc.relation.ispartofVirology Journal
dc.subjectCoronavirusen_US
dc.subjectInnate immunityen_US
dc.subjectInterferonen_US
dc.subjectIRF3en_US
dc.subjectSevere acute respiratory syndromeen_US
dc.titleThe SARS coronavirus papain like protease can inhibit IRF3 at a post activation step that requires deubiquitination activityen_US
dc.typeArticleen_US
dc.identifier.doi10.1186/s12985-014-0209-9
dc.identifier.pmid25481026
dc.identifier.ispublishedNo


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