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1、VIROLOGY141,89-101(19%)InVivaandinVitroModelsofDemyelinatingDiseaseXl.TropismandDifferentiationRegulatetheInfectiousProcessofCoronavirusesinPrimaryExplantsoftheRatCNSS.BEUSHAUSENANDS.DALESCytobiologyGroup,DepartmentofMkobbhgyandImmundogy,Unive-rsityofWesternOntario,London,OntarioN6A5C1,CanadaRe
2、ceivedAugust20,1984;acceptedOctober25,1984Thecoronaviruses,ubiquitousinmammals,includingman,manifestserotype-relatedpredelictionfordifferenttissues.ThispresentationdealswithspecificityofthemurineviseerotropicMHV3andneurotropicJHMVforexplantedcellsfromtheCNSofnewborn,inbred,Wistar-Furthrats.Anun
3、ambiguoustropismofMHV3forastrocytesandJHMVforoligodendrocytesisdemonstrated.Withthelattercell-virusinteraction,relativelysmalldifferencesinspatialdensityofoligodendrocytesinfluenceprofoundlythedurationofpersistenceandvirusyield.Theinvitrotemporalprogramofoligoden-drocytedifferentiation,monitore
4、dbyinductionofamyelin-relatedenzyme,2:3-cyclicnucleotide-3-phosphohydrolase,correspondstothatoccurringintivo(F.A.MeMorris,J.Neurochem41,506-515,1933).Itiscompletewithin15-21daysandiscoincidentwiththeonsetofinsusceptibilitytodiseasecausedbyJHMV.Experimentalelevationofintracellularcyclic-AMPlevel
5、s,presumedtoreflectoligodendrocytedifferentiation,likewisesuppressesJHMVreplicationwithoutaffectingthatofMHV3inastrocytes.OnthebasisofthesedataitisconcludedthatinvitrointeractionofJHMVwitholigodendrocytesreflectsaccuratelytheinvivahostcontroloverthetropismandexpressionofthisvirus,therebyeffecti
6、ngtheprogressive,demyelinativedisease,process.019%AcademicPress.Inc.INTRODUCTIONpaticnecrosiswhiletheneurotropicstrain,JHMV,aCNSdisease(VirelizieretaL,Thecoronaviruses(CV)areawidely1975).InfectionoftheratCNS,beforedisseminatedgroupofagentsinfectingweaning,mayresultindevelopmentofananimals,inclu
7、dingman(Tyrrellet&,acute,fatalencephalitisoraslowlypro-1965;Hamreetal,1966).Capabilityofgressive,chronicandsometimesremitting,somerodentCVtypestoinduceapro-paralyticdiseasecharacterizedbyfociofgressivedymyelinationinthecentralner-
