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1、VIROLOGY233,260–270(1997)ARTICLENO.VY978613KineticsofCytokinemRNAExpressionintheCentralNervousSystemFollowingLethalandNonlethalCoronavirus-InducedAcuteEncephalomyelitis,1,,BeatrizParra,*DavidR.Hinton,†‡MarkT.Lin,‡DanielJ.Cua,†andStephenA.Stohlman*†*DepartmentofMolecularMi
2、crobiologyandImmunology,†DepartmentofNeurology,and‡DepartmentofPathology,UniversityofSouthernCaliforniaSchoolofMedicine,LosAngeles,California90033ReceivedMarch3,1997;returnedtoauthorforrevisionMarch31,1997;acceptedApril22,1997Thepotentialrole(s)ofcytokinesinthereductionof
3、infectiousvirusandpersistentviralinfectioninthecentralnervoussystemwasexaminedbydeterminingthekineticsofcytokinemRNAexpressionfollowinginfectionwiththeneurotropicJHMstrainofmousehepatitisvirus.Micewereinfectedwithanantibodyescapevariantwhichproducesanonlethalencephalomyel
4、itisandcomparedtoaclonalviruspopulationwhichproducesafulminantfatalencephalomyelitis.InfectionwithbothvirusesinducedtheaccumulationofmRNAsassociatedwithTh1-andTh2-typecytokines,includingIFN-g,IL-4,andIL-10.PeakmRNAaccumulationswerecoincidentwiththeclearanceofvirusandthere
5、wasnoobviousdifferencesbetweenlethallyandnonlethallyinfectedmice.TNF-amRNAwasinducedmorerapidlyinlethallyinfectedmicecomparedtomiceundergoinganonfatalencephalomyelitis.RapidtransientincreasesinthemRNAsencodingIL-12,iNOS,IL-1a,IL-1b,andIL-6occurredfollowinginfection.Nonlet
6、halinfectionswereassociatedwithincreasedIL-12,IL-1b,andearlierexpressionofIL-6,whilelethalinfectionswereassociatedwithincreasediNOSandIL-1amRNA.ThesedatasuggestarapidbutdifferentialresponsewithinthecentralnervoussystemcellstoinfectionbydifferentJHMVvariants.However,neithe
7、rtheaccumulationnorkineticsofinductionprovideevidencetodistinguishlethalinfectionsfromnonlethalinfectionsleadingtoapersistentinfection.AccumulationofbothTh1andTh2cytokinesinthecentralnervoussystemofJHMV-infectedmiceisconsistentwiththeparticipationofbothcytokinesandcellimm
8、uneeffectorsduringresolutionofacuteviral-inducedencephalomyelitis.q1997AcademicPressINTRODUCTION
