AntiviralimmunityPaulZhouInstitutPasteurofShanghaiVirusesthatinitiateinfectionviatheskin,eye,orgenitaltractSiteofinfectionMethodofinfectionVirusfamilyExamplesSkinMinorbreaks/cutsHepadnaviridaeHepatitisBHerpesviridaeHerpessimplex1PapovaviridaePapillomavirusPoxviridaeVacciniaAnimalbiteHerpesviridaeHerpesmonkeyBRhabdoviridaeRabiesVectorbiteBunyaviridaeRiftValleyfeverFlaviviridaeYellowfever,DengueReoviridaeColoradotickfeverTogaviridaeEasternencephalitisInjectionFlaviviridaeHepatitisCHepadnaviridaeHepatitisBHerpesviridaeCytomegalovirusRetroviridaeHIV,HTLV-1ConjunctivaContactAdenoviridaeAdenovirusPicornaviridaeEnterovirus70GenitaltractContactFlaviviridaeHepatitisCHepadnaviridaeHepatitisBHerpesviridaeHerpessimplex2PapovaviridaePapillomavirusRetroviridaeHIVVirusesthatinitiateinfectionviatherespiratorytractLocalizationofdiseaseVirusfamilyExampleUpperrespiratorytractAdenoviridaeAdenovirusPicornaviridaeRhinoviruses,someenterovirusesLowerrespiratorytractBunyaviridaeSinNombreCoronaviridaeCoronavirusOrthomyxoviridaeInfluenzaParamyxoviridaeParainfluenza,RSVGeneralizedsystemicdiseasewithoutinitialrespiratorysymptomsArenaviridaeLassafeverBunyaviridaeHantaanvirusHerpesviridaeVaricella,cytomegalovirusPapovaviridaeBKandJCvirusesParamyxoviridaeMumps,measlesPoxviridaeSmallpox(extinct)TogaviridaeRubellaVirusesthatinitiateinfectionviathealimentarytractSiteofinfectionVirusfamilyExamplesMouth/oropharynxHerpesviridaeHerpessimplex,Epstein-Barrvirus,cytomegalovirusIntestinaltractProducingenteritisAdenoviridaeAdenovirus40,41AstroviridaeAstrovirusCaliciviridaeNorwalkagentReoviridaeRotavirusProducinggeneralizedPicornaviridaePoliovirusdiseaseusuallywithoutHepatitisAentericillnessUsuallysymptomlessAdenoviridaeSomeadenovirusesPicornaviridaeEnterovirusReoviridaeReovirusRelationshipbetweeninitialsiteofviralinfectionanddiseaseproductionSiteofinfectionLocalSystemicOropharynxCytomegalovirusEpstein-BarrvirusHerpessimplex1RespiratorytractInfluenzavirusMeaslesRSVMumpsRhinovirusRubellaVaricellaLassaIntestinaltractRotavirusNorwalkHepatitisAPolioGenitaltractPapillomavirusHepatitisBHepatitisCHIVVirusesthatinfectcirculatingbloodcellsCelltypeVirusMonocytesCMVDengueEbolaHIVLassaMeaslesRubellaYellowfeverBcellsEBVTcellsHIVHumanT-cellleukemiavirusI/IIHumanherpes6,7ErythroblastsColoradotickfeverViraltransmissionModeoftransmissionExampleCommentAerosol/salivarespiratoryorInfluenzavirusTransmissionissalivaryspreadEBVdifficulttocontrolMeaslesMumpsFecal-hand-mouthspreadPolioControllablebypublicHepatitisAhealthmeasuresRotavirusVenerealspreadHSVControllablebyHPVappropriateprecautionsHIVZoonosesInsecttohumanDengue,RabiesHumaninfectioncanbeAnimaltohumanLassa,Hanta,controlledbycontrollingAnimaltoInsecttohumanYellowfevervectors(insects)and/orbycontrollinganimalinfectionInnateimmunityagainstviruses•Cells–immunecellsandnon-immunecells•Receptors–TRL3,7,and8andC-typelectinreceptors:MMR,DEC205,Langerin,BDCA-2,andDC-SIGN•Cytokinesandtheirmechanisms–Directandindirect•Regulations–PositiveandnegativeCytokineswithpotentialtopromoteinnateimmunityduringviralinfectionsFunctionsCytokineNonadaptivecellsourcesAntiviralImmunoregulatoryIFN-a/bMonocytes/macrophagesXXXXXXVirus-infectedimmuneandnonimmunecellsTNFMonocytes/macrophagesXXXXXXNKCellsOthernonimmunecellsIFN-gNKCellsXXXXXXIL-12Monocytes,macrophagesXXXXXPMN’s,dendriticcellsIL-1a,IL-1bMonocytes/macrophages?XXOthernonimmunecellsIL-6Monocytes/macrophages?XXOthernonimmunecellsIGIFMonocytes/macrophages?XXOthernonimmunecellsIL-15Monocytes/macrophages?XXOthernonimmunecellsIL-10Monocytes/macrophages?XXOthernonimmunecellsTGF-bMonocytes/macrophagesXXOthernonimmunecellsAdaptiveimmunityagainstvirusesEffectorsystemRecognitionmoleculeMechanismofviralcontrolAntibodySurfaceglycoproteinsorNeutralizationofvirusoutercapsidproteinsOpsonizationofvirusparticlesViralglycoproteinsACDCandADCofvirusinfectedcellsexpressedonmembraneDownregulationofintracellularviralgeneofinfectedcellsexpressionCD4TcellsViralpeptides(15mers)ViralpeptidederivedfromanyexogenouspresentedbyMHCIIproteins(surface,internal,ornonstructural)Releaseofantiviralcytokines(IFN-g,TNF)Activation/recruitmentofmacrophages.HelpforantiviralantibodyproductionHelpforCD8CTLresponsesKillviralinfectedcellsCD8TcellsViralpeptides(8mers)ViralpeptidewhichusuallyarederivedpresentedbyMHCIfromendogenousviralproteinsCrossprimingforexogenouspeptideKillingofvirus-infectedcellsReleaseofantiviralcytokines(IFN-g,TNF)Activation/recruitmentofmacrophagesHumoralresponsetoacuteviralinfectioninhumansExampleSerumantibody(yr)Mucosalantibody(mo).SystemicinfectionsDengue32Yellowfever75Measles65Mumps12Polio40HepatitisA25Smallpox40Vaccinia15Rubella14MucosalinfectionsCoronavirus12Influenzavirus30Respiratorysyncytialvirus3Rotavirus12Modelsoflong-termantibodyproductionMechanismRe-exposuretovirus-Persistentviralinfection-Immunecomplexesonfolliculardendriticcells-Cross-reactivitytoselforenvironmentalantigens-IdiotypicnetworksLonglivedplasmacellsCommentsConventionalmodelsformaintaininghumoralimmunityinwhichshort-livedplasmacellsareco