Gamma-Irradiated Influenza Virus Uniquely Induces IFN-I Mediated Lymphocyte Activation Independent of the TLR7MyD88 Pathway 英文参考文献.docVIP

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Gamma-Irradiated Influenza Virus Uniquely Induces IFN-I Mediated Lymphocyte Activation Independent of the TLR7MyD88 Pathway 英文参考文献.doc

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Gamma-Irradiated Influenza Virus Uniquely Induces IFN-I Mediated Lymphocyte Activation Independent of the TLR7MyD88 Pathway 英文参考文献

Gamma-IrradiatedInfluenzaVirusUniquelyInducesIFN-I MediatedLymphocyteActivationIndependentofthe TLR7/MyD88Pathway YoichiFuruya1¤,JenniferChan2,En-ChiWan2,AulikkiKoskinen1,KerrilynR.Diener3,4,JohnD. Hayball3,4,5,MatthiasRegner1,ArnoMu¨llbacher1,MohammedAlsharifi1,2* 1DepartmentofEmergingPathogensandVaccines,TheJohnCurtinSchoolofMedicalResearch,AustralianNationalUniversity,Canberra,AustralianCapitalTerritory, Australia,2DepartmentofMicrobiologyandImmunology,SchoolofMolecularandBiomedicalScience,TheUniversityofAdelaide,Adelaide,SouthAustralia,Australia, 3Experimental Therapeutics Laboratory, Hanson Institute, Adelaide, South Australia, Australia, 4Sansom Institute, The University of South Australia, Adelaide, South Australia,Australia,5DepartmentofMedicine,TheUniversityofAdelaide,Adelaide,SouthAustralia,Australia Abstract Background:Wehaveshownpreviouslyinmice,thatinfectionwithliveviruses,includinginfluenza/AandSemlikiForest virus(SFV),inducessystemicpartialactivationoflymphocytes,characterizedbycellsurfaceexpressionofCD69andCD86, butnotCD25.Thispartiallymphocytesactivationismediatedbytype-Iinterferons(IFN-I).Importantly,wehaveshownthat c-irradiatedSFVdoesnotinduceIFN-Iandtheassociatedlymphocyteactivation. PrincipalFindings:Herewereportthat,incontrasttoSFV,c-irradiatedinfluenzaAviruselicitspartiallymphocyteactivation invivo.Furthermore,weshowthatwhenusinginfluenzavirusesinactivatedbyavarietyofmethods(UV,ionisingradiation and formalin treatment), as well as commercially available influenza vaccines, only c-irradiated influenza virus is able to triggerIFN-I-dependentpartiallymphocyteactivationintheabsenceoftheTLR7/MyD88signallingpathways. Conclusions:Ourdatasuggestanimportantmechanismfortherecognitionofc-irradiatedinfluenzavaccinebycytosolic receptors, which correspond with the ability of c-irradiated influenza virus to induce cross-reactive and cross-protective cytotoxicTcellresponses. Citation: Furuya Y, Chan J, Wan E-C, Koskinen A, Diener KR, et al. (2011) Gamma-Irr