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1、_ArchivesArchVirot(1991)121:89-100Virology©Springer-Verlag1991PrintedinAustriaTheroleofgammainterferonininfectionofsusceptiblemicewithmurinecoronavirus,MHV-JHMAbigailL.Smitht'2,S.W.Barthold1,M.S.deSouza1'2,andKimBottomly31SectionofComparativeMedicine,2DepartmentofEpidemiologyandPubl
2、icHealth,and3HowardHughesMedicalInstituteandSectionofImmunobiology,YaleUniversitySchoolofMedicine,NewHaven,Connecticut,U.S.A.AcceptedMarch31,1991Summary.InfectionofBALB/cmicewithmousehepatitisvirus,strainJHM(MHV-JHM),atanyofseveralintervalsrelativetoovalbumin(OVA)admin-istrationresu
3、ltedinelevatedOVA-specificIgG2atiters.Sincegammainterferon(IFN)hasbeenimplicatedasanup-regulatorofIgG2aproduction,attemptsweremadetodeterminewhetherlevelsofthiscytokineweremodifiedinseraofinfectedmice.SerumIFN-ywasnotdetected,buttreatmentofMHV-JHM-infectedmicewithmonoclonalanti-IFN-
4、?antibodyresultedinhighmortalitywithdecreasedsurvivaltimes,enhancedvirustitersinliverandspleen,andmoreseverevirus-associatedpathology,comparedtomock-treated,infectedmice.ImmunotherapywithrecombinantIFN-7ameliorateddiseaseasreflectedbymortalityratesandvirustitersintargetorgans.Introd
5、uctionMiceinoculatedwithsolubleproteinantigenspreferentiallyproduceIgG1andIgG3specifictothatantigen[3,7].Incontrast,infectionofmicewithanyofseveralvirusesenhancestheIgG2aresponsebothtotheinfectingvirusandtoimmunizingsolubleproteinantigens[6-8].Gammainterferon(IFN),acytokinepreferent
6、iallyproducedbytheTh1subsetofCD4+Tcells[5],stimulatesproductionofIgG2abyBlymphocytesactivatedinvitroandinvivoandinhibitsIgG1secretion[12,30,31].Thus,ithasbeenpostulatedthattheimmuneresponsetriggeredbyvirusesmainlyactivatestheTh1subsetofhelperTcells[7-].Mousehepatitisvirus(MHV)isasin
7、gularnameforagroupofcoronaviruses,familyCoronaviridae,infectinglaboratorymiceworldwideathighprevalence[18,20,22].MiceinfectedwithMHVcanexhibitaberrantimmuneresponsesthatinterferewiththeirusefulnessinbiomedicalresearch[4,9,10,27-29].90AbigailL.Smithetal.Coutelierandco-workers[7]showe
8、dalteredprotein-spe
