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1、CHAPTER10THEMOLECULARBIOLOGYOFCORONAVIRUSESBRIANW.J.MAHYTheAnimalVirusResearchInstitute,Pirbright,U.K.INTRODUCTIONThefamilyCoronaviridaeconsistsofelevenviruseswhichinfectvertebratesandcausearangeofdiseasesmostlyaffectingtherespiratoryorthegastro?intestinaltract(1).Thenamecoronavirusw
2、ascoinedbyTyrrelel01.(2)onthebasisofthecharacteristiccoronaofwidelyspacedbulboussurfaceprojections,12-24nmlong,seeninelectronmicrographsoftheseviruses(Figure1).Morerecently,ithasbecomeclearthatmembersoftheCoronaviridaeshareanumberofmolecularbiologicalfeatureswhichconstituteauniquerep
3、licationstrategyandsetthesevirusesapartfromothervirusgroups.Thesefeaturesmayunderliethefascinatingbiologicalpropertiesofcertainmurinecoronaviruseswhichprovideoneofthebestavailablemodelsforhumandemyelinatingneurologicaldiseases(3).1.BIOLOGICALPROPERTIESCoronavirusesaffectseveralspecie
4、s,includingchicken,cattle,pigs,dogs,cats,mice,ratsandman(Table1).Althoughacuterespiratoryorentericdiseasesarecommonfeaturesofcoronavirusinfections,thereareseveralexamplesofchronicpersistentinfections,andthesemayinvolvethecentralnervoussystem.Mousehepatitisvirus(MHV)existsinfourstrain
5、s,oneofwhich(MHV-4,JHMstrain)caninducechronicorrecurrentcentralnervoussystemdemyelinationaswellasencephalomyelitisinbothmiceandrats(3-5).Theexactoutcomeofinfectiondependsupontheageandstrainoftherodenthostaswellasthedoseandrouteofinoculation.ThereisevidencethatpathogenicityofJHMvirusi
6、sgeneticallycon?trolled,sincevirusmutantscausingdemyelinationratherthanencephalitiscanbeselectedasIsmutants(6)orusingmonoclonalantibodies(7).Perhapsthemostin?terestingrodentmodelistheinfectionof10-15dayoldratswithamutantofJHM239R.P.Bercoff(ed.),TheMolecularBasisofViralReplication?Ple
7、numPress,NewYork1987240B.W.J.MAHYFigure1.Virionsofavianinfectiousbronchitisvirus(electronmicrographcourtesyofDr.CavanaghandJ.K.A.Cook).virus(ts43),whichresultsinahighproportionofpersistentlyinfectedanimalsthatdevelopasubacuterelapsing-remittingdemyelinatingdiseasewithcloseparallelsto
8、mUltiplescle
