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1、VIROLOGY170,556-560(1969)SHORTCOMMUNICATIONSSpreadofaNeurotropicMurineCoronavirusintotheCNSviatheTrigeminalandOlfactoryNervesSTANLEYPERLMAN,*+GARYJACOBSEN,*ANDADELAFIFI*+§DepartmentsofPediatrics,tMicrobiology,*Anatomy,and§Neurology,UniversityofIowa,IowaCity,Iowa52242ReceivedJanuary17,1989;acceptedMa
2、rch2.1989Therouteofentryintothecentralnervoussystem(CNS)ofmostneurotropicviruseshasnotbeenestablished.Thecoronavirus,mousehepatitisvirusstrainJHM(MHV-JHM).causesacuteencephalomyelitisandacuteandchronicdemyelinatingdiseasesandisanimportantmodelsystemforvirus-inducedneurologicaldisease.SucklingC57BU6m
3、iceinfectedintranasallywithMHV-JHMdevelopeithertheacuteencephalomyelitisoralateonset,symptomaticdemyelinatingencephalomyelitis,dependingonwhethertheyarenursedbyunimmunizedorimmunizeddams.AnalysisbyinsituhybridizationwasusedtodeterminetherouteofentryofMHV-JHMintotheCNSinthesemice.Atearlytimes,viralRN
4、Awasdetectedonlyinthetrigeminalandolfactorynervesandintheirimmediateconnectionsinallmice.Afewdayslater,MHV-JHMRNAwasfoundthroughoutthebraininmicedyingoftheacuteencephalomyelitis,butremainedconfinedtotheentrysitesinmicewhichdidnotdevelopacutedisease.TheseresultssuggestthatMHV-JHMenterstheCNSviaaninte
5、rneuronalrouteinallmice,butthatthepresenceofmaternalantibodypreventsthedisseminationofvirusviaextracellularfluid.Inaddition,MHV-JHMmayestablishlow-levelpersistenceinthetrigeminalorolfactorynerveorinoneofitsconnectionsinmicethatdonotdevelopacuteencephalomyelitis.o1~8sAcademicPress.Inc.Coronaviruses,p
6、ositive-strandedRNAviruses,areinthebrainstemandspinalcordofallmicewiththelateabletoinfectpersistentlymanytypesofanimals(1,2).onsetdisease(16-l7).Neurotropicstrainsofthemurinecoronavirus,mouseInthisreport,weusedthemethodofinsituhybrid-hepatitisvirus(MHV),causeacuteencephalomyelitisizationtolocalizevi
7、rus-specificRNAintheCNSatearlyandacuteandchronicdemyelinatingdiseasesinsus-timesafterintranasalinfection.Atafewdaysp.i.,MHV-ceptiblerodents(2-70).Forthisreason,miceorratsJHMRNAwasdetectedinthetrigemin