RIG-I, MDA5 and TLR3 Synergistically Play an Important Role in Restriction of Dengue Virus Infection 英文参考文献.docVIP

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RIG-I, MDA5 and TLR3 Synergistically Play an Important Role in Restriction of Dengue Virus Infection 英文参考文献.doc

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RIG-I, MDA5 and TLR3 Synergistically Play an Important Role in Restriction of Dengue Virus Infection 英文参考文献

RIG-I,MDA5andTLR3SynergisticallyPlayanImportant RoleinRestrictionofDengueVirusInfection A.M.A.Nasirudeen1*.,HuiHuiWong1.,PeilingThien2,ShengliXu3,Kong-PengLam3,DingXiang Liu1,2 * 1InstituteofMolecularandCellBiology,Singapore,Singapore,2SchoolofBiologicalSciences,NanyangTechnologicalUniversity,Singapore,Singapore,3Immunology Group,BioprocessingTechnologyInstitute,Singapore,Singapore Abstract Denguevirus(DV)infectionisoneofthemostcommonmosquito-borneviraldiseasesintheworld.Theinnateimmune system is importantfor theearly detectionofvirus andformounting acascade of defensemeasureswhich include the productionoftype1interferon(IFN).Hence,athoroughunderstandingoftheinnateimmuneresponseduringDVinfection wouldbeessentialforourunderstandingoftheDVpathogenesis.Arecentapplicationofthemicroarraytodenguevirus type1(DV1)infectedlungcarcinomacellsrevealedtheincreasedexpressionofbothextracellularandcytoplasmicpattern recognitionreceptors;retinoicacidinduciblegene-I(RIG-I),melanomadifferentiationassociatedgene-5(MDA-5)andToll- likereceptor-3(TLR3).TheseintracellularRNAsensorswerepreviouslyreportedtosenseDVinfectionindifferentcells.In thisstudy,weshowthattheyarecollectivelyinvolvedininitiatinganeffectiveIFNproductionagainstDV.Cellssilencedfor these genes were highly susceptible to DV infection. RIG-I and MDA5 knockdown HUH-7 cells and TLR3 knockout macrophageswerehighlysusceptibletoDVinfection.WhencellsweresilencedforonlyRIG-IandMDA5(butnotTLR3), substantialproductionofIFN-bwasobserveduponvirusinfectionandviceversa.Highsusceptibilitytovirusinfectionledto ER-stress induced apoptosis in HUH-7 cells. Collectively, our studies demonstrate that the intracellular RNA virus sensors (RIG-I,MDA5andTLR3)areactivateduponDVinfectionandareessentialforhostdefenseagainstthevirus. Citation:NasirudeenAMA,WongHH,ThienP,XuS,LamK-P,etal.(2011)RIG-I,MDA5andTLR3SynergisticallyPlayanImportantRoleinRestrictionofDengue VirusInfection.PLoSNeglTropDis5(1):e926.doi:10.1371/journal.pntd.0000926 Editor:EvaHarr