冠状病毒Coronavirusl论文-1984 Adaptation of Coronavirus JHM to Persistent Infection of Murine Sac(-) Cells.pdf

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1、J.gen.Virol.(1984),65,915-924.PrintedinGreatBritain915Keywords:coronavirusJHM/persistentinfection/adaptation/virulenceAdaptationofCoronavirusJHMtoPersistentInfectionofMurineSac(-)CdlsByHERBERTN.BAYBUTT,tHELMUTWEGE,*MICHAELJ.CARTER:~ANDVOLKERTERMEULENlnstitutJ~

2、rVirologicundImmunbiologiederUniversiti~tWi~rzburg,VersbacherStrasse7,D-8700Wftrzburg,FederalRepublicofGermany(Accepted1February1984)SUMMARYCoronavirusescanestablishpersistentinfectionsinthecentralnervoussystemofrodents,andtheseareassociatedwithdemyelinatingen

3、cephalomyelitis.Theeffectsofpersistenceonthevirusaredifficulttostudyinvivobutmayhaveacrucialinfluenceonthecourseofinfection.WethereforeproducedapersistentinfectioninvitrousingtheneurotropiccoronavirusJHM,inordertoinvestigatetheeventsunderlyingtheestablishmento

4、fsuchaninfectionandtheadaptationofthevirustopersistence.Thepersistentinfectionwasmaintainedforover115passagesandcontinuedtoreleasehighlevelsofinfectiousvirus.Duringthe18monthsofculturethenumberofcellsexpressingvirusantigendetectedbyindirectimmunefluorescencede

5、creasedto40~.Analysisshowedthatthecarriedviruscontainedasignificantproportionofheterogeneoustemperature-sensitivemutants.Allvirusclonesisolatedpossessedthecapacitytoinduceamoreproductivegrowthcycle,alesspronouncedcytopathiceffectandshowedamuchreducedneurovirul

6、encewheninoculatedintonewbornandweanlingrats.Evidenceforstructuralchangesinvolvingthesurfacepeplomerprotein(E2)wasobtainedusinghybridomaantibodies,whichneutralizedtheparentalJHMvirusbutnottheJHM-Pivirus.Defectiveinterferingparticlesandinterferonactivitieshaveb

7、eenexcludedaspossibleagentsinstrumentalintheestablishmentandmaintenanceofthechronicinfection,andwesuggestthattheemergenceofvirusvariantsofloweredvirulenceiscentraltotheseprocesses.INTRODUCTIONManyviruseshavebeenimplicatedindiseasesofthehumancentralnervoussyste

8、m(terMeulen&Siddell,1981).Cheereretal.(1949)firstdescribedadelayedencephalomyelitisassociatedwithdemyelinationinratsinfectedwiththecoronavirusJHM.Theseearlyobservationshaverecently