RIG-I Mediates Innate Immune Response in Mouse Neurons Following Japanese Encephalitis Virus Infection 英文参考文献.docVIP

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RIG-I Mediates Innate Immune Response in Mouse Neurons Following Japanese Encephalitis Virus Infection 英文参考文献.doc

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RIG-I Mediates Innate Immune Response in Mouse Neurons Following Japanese Encephalitis Virus Infection 英文参考文献

RIG-IMediatesInnateImmuneResponseinMouse NeuronsFollowingJapaneseEncephalitisVirusInfection ArshedNazmi,KallolDutta,AnirbanBasu* NationalBrainResearchCentre,Manesar,Haryana,India Abstract Background:NeuroinflammationassociatedwithJapaneseencephalitis(JE)ismainlyduetotheactivationofglialcellswith subsequent release of proinflammatory mediators from them. The recognition of viral RNA, in part, by the pattern recognitionreceptorretinoicacid-induciblegeneI(RIG-I)hasbeenindicatedtohavearoleinsuchprocesses.Eventhough neuronsarealsoknowntoexpressthisreceptor,itsroleafterJEvirus(JEV)infectionsisyettobeelucidated. Methodology/Principal Findings: Uponinfecting murine neuroblastoma cells andprimary cortical neurons withJEV the expression profile of keyproinflammatory cyto/chemokines were analyzed by qRT-PCR andbead array, both before and afterablationofRIG-I.ImmunoblottingwasperformedtoevaluatethelevelsofkeymoleculesdownstreamtoRIG-Ileading to production of proinflammatory mediators. Changes in the intracellular viral antigen expression were confirmed by intracellular staining and immunoblotting. JEV infection induced neuronal expression of IL-6, IL-12p70, MCP-1, IP-10 and TNF-ainatime-dependentmanner,whichshowedsignificantreductionuponRIG-Iablation.MoleculesdownstreamtoRIG- IshowedsignificantchangesuponJEV-infection,thatweremodulatedfollowingRIG-Iablation.AblationofRIG-Iinneurons alsoincreasedtheirsusceptibilitytoJEV. Conclusions/Significance:Inthisstudyweproposethatneuronsareoneofthepotentialsourcesofproinflammatorycyto/ chemokinesinJEV-infectedbrainthatareproducedviaRIG-Idependentpathways.AblationofRIG-Iinneuronsleadsto increasedviralloadandreducedreleaseofthecyto/chemokines. Citation: Nazmi A, Dutta K, Basu A (2011) RIG-I Mediates Innate Immune Response in Mouse Neurons Following Japanese Encephalitis Virus Infection. PLoS ONE6(6):e21761.doi:10.1371/journal.pone.0021761 Editor:BradleyS.Schneider,GlobalViralForecastingInitiative,UnitedStatesofAmerica ReceivedMarch8,2011;A