Influenza A Virus NS1 Protein Inhibits the NLRP3 Inflammasome

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dc.contributor.authorCheong, Woo-Changko
dc.contributor.authorKang, Hye-Riko
dc.contributor.authorYoon, Hyunyeeko
dc.contributor.authorKang, Suk-Joko
dc.contributor.authorTing, Jenny P. -Y.ko
dc.contributor.authorSong, Moon Jungko
dc.date.accessioned2015-06-25T06:24:32Z-
dc.date.available2015-06-25T06:24:32Z-
dc.date.created2015-06-09-
dc.date.created2015-06-09-
dc.date.issued2015-05-
dc.identifier.citationPLOS ONE, v.10, no.5-
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10203/199057-
dc.description.abstractThe inflammasome is a molecular platform that stimulates the activation of caspase-1 and the processing of pro-interleukin (IL)-1 beta and pro-IL-18 for secretion. The NOD-like receptor family, pyrin domain containing 3 (NLRP3) protein is activated by diverse molecules and pathogens, leading to the formation of the NLRP3 inflammasome. Recent studies showed that the NLRP3 inflammasome mediates innate immunity against influenza A virus (IAV) infection. In this study, we investigated the function of the IAV non-structural protein 1 (NS1) in the modulation of NLRP3 inflammasome. We found that NS1 proteins derived from both highly pathogenic and low pathogenic strains efficiently decreased secretion of IL-1 alpha and IL-18 from THP-1 cells treated with LPS and ATP. NS1 overexpression significantly impaired the transcription of proinflammatory cytokines by inhibiting transactivation of the nuclear factor-kappa B (NF-kappa B), a major transcription activator. Furthermore, NS1 physically interacted with endogenous NLRP3 and activation of the NLRP3 inflammasome was abrogated in NS1-expressing THP-1 cells. These findings suggest that NS1 downregulates NLRP3 inflammasome activation by targeting NLRP3 as well as NF-kappa B, leading to a reduction in the levels of inflammatory cytokines as a viral immune evasion strategy.-
dc.languageEnglish-
dc.publisherPUBLIC LIBRARY SCIENCE-
dc.subjectPRE-MESSENGER-RNAS-
dc.subjectNF-KAPPA-B-
dc.subjectADAPTIVE IMMUNITY-
dc.subjectHUMAN MACROPHAGES-
dc.subjectNUCLEAR EXPORT-
dc.subjectCELL-DEATH-
dc.subjectIN-VIVO-
dc.subjectINTERFERON-
dc.subjectINNATE-
dc.subjectGENE-
dc.titleInfluenza A Virus NS1 Protein Inhibits the NLRP3 Inflammasome-
dc.typeArticle-
dc.identifier.wosid000354916100069-
dc.identifier.scopusid2-s2.0-84929346755-
dc.type.rimsART-
dc.citation.volume10-
dc.citation.issue5-
dc.citation.publicationnamePLOS ONE-
dc.identifier.doi10.1371/journal.pone.0126456-
dc.contributor.localauthorKang, Suk-Jo-
dc.contributor.nonIdAuthorCheong, Woo-Chang-
dc.contributor.nonIdAuthorKang, Hye-Ri-
dc.contributor.nonIdAuthorYoon, Hyunyee-
dc.contributor.nonIdAuthorTing, Jenny P. -Y.-
dc.contributor.nonIdAuthorSong, Moon Jung-
dc.description.isOpenAccessY-
dc.type.journalArticleArticle-
dc.subject.keywordPlusPRE-MESSENGER-RNAS-
dc.subject.keywordPlusNF-KAPPA-B-
dc.subject.keywordPlusADAPTIVE IMMUNITY-
dc.subject.keywordPlusHUMAN MACROPHAGES-
dc.subject.keywordPlusNUCLEAR EXPORT-
dc.subject.keywordPlusCELL-DEATH-
dc.subject.keywordPlusIN-VIVO-
dc.subject.keywordPlusINTERFERON-
dc.subject.keywordPlusINNATE-
dc.subject.keywordPlusGENE-
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