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1、NeuroparhologyandAppliedNeurobiology1991,17,469-484Coronavirusinducedprimarydemyelination:indicationsfortheinvolvementofahumoralimmuneresponseF.ZIMPRICH*,J.WINTER?,H.WEGETANDH.LASSMA"*$*ResearchUnitforExperimentNeuropathology,AustrianAcademyofSciences,Vienna,Austria,tlnstit
2、uteforVirologyandImmunology,UniversityofWurzburg,Wurzburg,Germanyand$NeurologicalInstitute,UniversityofVienna,Vienna,AustriaZIMPRICHF.,WINTERJ.,WEGEH.&LASSMANNH.(1991)NeuropathologyandAppliedNeurobiology17,469-484Coronavirusinducedprimarydemyelination:indicationsfortheinvol
3、vementofahumoralimmuneresponseCoronavirusMHV-JHMinfectionofrodentscanresultindemyelinatingencephalomyelitis.WeanalysedhistologicalchangesinducedbycoronavirusMHV-JHMinfectioninLewisrats.Besidesanacutedisease(AE),chronicpanencephalitis(CPE)andsubacutedemyelinatingencephalomye
4、litis(SDE)wereinduced.Thesediseasetypesweredifferentiatedbytheincu-bationperiod,thelocalizationoflesions,thetypeoftissuedamageanddistributionofvirusantigen.InAEandCPE,virusantigenwasdetectedinneurons,astrocytesandoligodendro-cytes,whereasinSDEneuronslackedvirusantigen.Viral
5、nucleocapsidprotein(N)waspresentinthecytoplasmandthespikeprotein(S)wasdisplayedonthesurfaceofinfectedneuralcells.However,expressionofSproteinrelativetoNproteinwasseverelyimpairedinSDElesions.Quantitativeanalysisofinfiltratinginflammatorycellsrevealedthatthenumberofmacro-pha
6、gesandTcellsweresimilarinlesionsofAE,CPEandSDE.Incontrasttothat,SDElesionscontainedasignificantlyhighernumberofIgG+Bcellsandplasmacells.InadditionactivedemyelinatingSDElesionsdisplayedanenhancedIgGcontentanddepositsofcomplementC9.Theseresultsindicatethatvirusinducedprimaryd
7、emyelinationcouldbeaconsequenceofantibodymediatedcytotoxicity.Furthermore,areductioninthenumberofcellsproducingspikeproteininthechronicformsofthediseaseindicatesdown-regulationofthisprotein,possiblymediatedbyanti-Santibodies.Keywords:coronavirus,MHV-JHM,spikeprotein,encepha
8、litis,demyelination,remyelination,humoralimmuneresponseINTRODUCTIONInflammatorydem