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1、J.gen.Virol.(1989),70,763-768.PrintedinGreatBritain763Keywords:murinehepatitisvirus/persistentinfection/hygromycinBAModelforPersistentMurineCoronavirusInfectionInvolvingMaintenanceviaCytopathicallyInfectedCellCentresByGEORGINAMACINTYRE,FREDWONGANDROBERTANDERSON*Depart
2、mentofMicrobiologyandInfectiousDiseases,UniversityofCalgary,Calgary,AlbertaT2N4N1,Canada(Accepted7November1988)SUMMARYTherelativelycellimpermeablehygromycinBwasfoundtoinhibitviralbutnotcellularproteinsynthesiswhenaddedtoculturesofmurinehepatitisvirus(MHV)-infectedormo
3、ck-infectedmouseL-2fibroblasts.Membranepermeability,asjudgedbyinfluxofsodiumions,haspreviouslybeendemonstratedtobeanMHVE2glycoprotein-mediated,cytopathiceffectofMHVinfectioninL-2cells.ItisthereforelikelythattheselectiveeffectofhygromycinBonviralproteinsynthesisisarefl
4、ectionofanincreaseddrugpenetrationintovirus-infectedcells.UsinghygromycinBasamarkerforMHV-indueedcellmembranecytopathology,theeffectsofdrugtreatmentonapersistentMHVinfectioninmouseLM-Kfibroblastswereinvestigated.MHVpersistenceinLM-Kcells,whichnormallyinvolvesasteadyst
5、ateinfectionof0.1to1%ofthecellsinculture,wasfoundtobecuredbyhygromycinBtreatment,asmeasuredbytheeliminationofinfectiousvirusfromthesupernatantmedium.HygromycinBalsoresultedintheeradicationofMHV-specificRNAfromLM-Kcells,arguingagainstthepresenceofanon-cytopathicallyorl
6、atentlyinfectedsubpopulationofcells.Murinecoronaviruses,typifiedbymurinehepatitisvirus(MHV)areabletoproduceinfectionsofeitheranacuteorpersistentnature.Nevertheless,themechanismsbywhichtheoutcomeofsuchinfectionisdeterminedremainpoorlyunderstood.Studiesincellculturehave
7、implicatedtheinvolvementofattenuatedMHVvariantssuchasheat-sensitive(Holmes&Behnke,1981),cold-sensitive(Stohlmanetal.,1979)andsmallplaque(Hiranoetal.,1981)mutants.Evidencefrominvivostudieshasalsobeenpresentedsuggestingthegenerationduringlong-termnervoussysteminfectiono
8、fvirusvariantswhichgiverisetoalteredmRNAs(Jacksonetal.,1984;Taguchietal.,1987).Otherstudies(Lucasetal.,1977,1978;Mizzenetal.
