Both STING and MAVS Fish Orthologs Contribute to the Induction of Interferon Mediated by RIG-I 英文参考文献.docVIP

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Both STING and MAVS Fish Orthologs Contribute to the Induction of Interferon Mediated by RIG-I 英文参考文献.doc

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Both STING and MAVS Fish Orthologs Contribute to the Induction of Interferon Mediated by RIG-I 英文参考文献

BothSTINGandMAVSFishOrthologsContributetothe InductionofInterferonMediatedbyRIG-I Ste′phaneBiacchesi*,EmilieMe′rour,AnnieLamoureux,JulieBernard,MichelBre′mont Unite′ deVirologieetd’ImmunologieMole′culaires,INRA,CRJ,Jouy-en-Josas,France Abstract Viralinfectionsaredetectedinmostcasesbythehostinnateimmunesystemthroughpattern-recognitionreceptors(PRR), thesensorsforpathogen-associatedmolecularpatterns(PAMPs),whichinducetheproductionofcytokines,suchastypeI interferons(IFN).RecentidentificationinmammalianandteleostfishofcytoplasmicviralRNAsensors,RIG-I-likereceptors (RLRs), and their mitochondrial adaptor: the mitochondrial antiviral signaling (MAVS) protein, also called IPS-1, highlight theirimportantroleintheinductionofIFNattheearlystageofavirusinfection.Morerecently,anendoplasmicreticulum (ER)adaptor:thestimulatorofinterferongenes(STING)protein,alsocalledMITA,ERISandMPYS,hasbeenshowntoplay apivotalroleinresponsetobothnon-self-cytosolicRNAanddsDNA.Inthisstudy,weclonedSTINGcDNAsfromzebrafish andshowedthatitwasanorthologtomammalianSTING.WedemonstratedthatoverexpressionofthisERproteininfish cellsledtoaconstitutiveinductionofIFNandinterferon-stimulatedgenes(ISGs).STING-overexpressingcellswerealmost fullyprotectedagainstRNAvirusinfectionwithastronginhibitionofbothDNAandRNAvirusreplication.Inaddition,we foundthattogetherwithMAVS,STINGwasanimportantplayerintheRIG-IIFN-inducingpathway.Thisreportprovidesthe demonstration that teleost fish possess a functional RLR pathway in which MAVS and STING are downstream signaling molecules of RIG-I. The Sequences presented in this article have been submitted to GenBank under accession numbers: ZebrafishSTING(HE856619);EPCSTING(HE856620);EPCIRF3(HE856621);EPCIFNpromoter(HE856618). Citation: Biacchesi S, Me′rour E, Lamoureux A, Bernard J, Bre′mont M (2012) Both STING and MAVS Fish Orthologs Contribute to the Induction of Interferon MediatedbyRIG-I.PLoSONE7(10):e47737.doi:10.1371/journal.pone.0047737 Editor:KarenL.Mossman,McMasterUniversity