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1、VIROLOGY213,482–493(1995)ActivationofAstrocytesintheSpinalCordofMiceChronicallyInfectedwithaNeurotropicCoronavirus,,1NINGSUN,*DANAGRZYBICKI,†RAYMONDF.CASTRO,‡SEANMURPHY,§andSTANLEYPERLMAN*‡Departmentsof*Pediatrics,†Pathology,‡Microbiology,and§Pharmacology,UniversityofIowa
2、,IowaCity,Iowa52242ReceivedJuly5,1995;acceptedSeptember8,1995MiceinfectedwiththeneurotropicJHMstrainofmousehepatitisvirus(MHV-JHM)developademyelinatingencephalomy-elitisseveralweeksafterinfection.Astrogliosisandinfiltrationofinflammatorycellsareprominentfindingsinthebrain
3、sandspinalcordsofinfectedmice.Inthisreport,astrocytesininfectedspinalcordswereanalyzedforexpressionofthreepleiotropiccytokines,TNF-a,IL-1b,andIL-6;Type2nitricoxidesynthase(iNOS);andMHCclassIandIIantigen.ThedatashowthatallthreecytokinesandiNOSareexpressedbyastrocytesinchro
4、nicallyinfectedspinalcords.Theseactivatedastrocytesarelocalizedtoareasofvirusinfectionanddemyelination,althoughmostoftheastrocytesexpressingtheseproteinsarenotMHV-infected.MHCclassIandIIantigencanbedetectedinthesespinalcordsaswell,butnotincellswiththetypicalmorphologyofas
5、trocytes.TNF-a,IL-6,andiNOSarealsoevidentinthebrainsofmicewithMHV-inducedacuteencephalitis,butinmarkedcontrasttotheresultsobtainedwiththechronicallyinfectedmice,mostofthecellsexpressingthesecytokinesoriNOShadthemorphologyofmacrophagesorothermononuclearcellsandveryfewappea
6、redtobeastrocytes.Additionally,astrocytesand,mostlikely,oligodendrocytesareinfectedinthespinalcordsofmicewithchronicdemyelination.Theseresultsareconsistentwitharoleforbothviralinfectionofglialcellsandhighlocalizedlevelsofproinflammatorycytokinesandnitricoxideinthedemyelin
7、atingprocessinmiceinfectedwithMHV-JHM.Theyalsoshowthatanalogouslytothehumandemyelinatingdisease,multiplesclerosis,astrocytesareamajorcellularsourceforthesecytokinesinmicewithchronic,butnotacutedisease.q1995AcademicPress,Inc.INTRODUCTIONacuteencephalitis,butavariablepercen
8、tage(40–90%)developthechronicdemyelinatingdiseasedescribedTheJHMstrainofmousehepatitisvirus(MHV-