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1、VIROLOGY183,647-657(1991)HeterogeneityofGeneExpressionoftheHemagglutinin-Esterase(HE)ProteinofMurineCoronavirusesKYOKOYOKOMORI,LISAR.BANNER,ANDMICHAELM.C.LAI’HowardHughesMedicalInstituteandDepartmentofMicrobiology,UniversityofSouthernCalifornia,SchoolofMedicin
2、e,LosAngeles,California90033ReceivedJanuary28,1991;acceptedApril25,1991Thehemagglutinin-esterase(HE)membraneglycoproteinispresentonlyinsomemembersofthecoronavirusfamily,includingsomestrainsofmousehepatitisvirus(MHV).IntheJHMstrainofMHV,expressionoftheHEgeneisv
3、ariableandcorrespondstothenumberofcopiesofaUCUAApentanucleotidesequencepresentatthe3’-endoftheleaderRNA.ThiscopynumbervariesamongMHVstrains,dependingontheirpassagehistory.TheJHMisolateswithtwocopiesofUCUAAintheirleaderRNAshowedahighlevelofHEexpression,whereast
4、heJHMisolatewiththreecopieshadalow-levelexpression.Inthisstudy,theanalysisofHEgeneexpressionwasextendedtootherMHVstrains.ThesynthesisofHEmRNAinthesevirusesalsocorrelateswiththecopynumberofUCUAAintheleaderRNAandtheparticularintergenicsequenceprecedingtheHEgene.
5、InoneMHVstrain,MHV-1,nodetectableHEmRNAwassynthesized,despitethepresenceofapropertranscriptioninitiationsignal.ThislackofHEmRNAexpressionwasconsistentwithaleaderRNAcontainingthreeUCUAAcopies.However,mutationsanddeletionswithinthecodingregionoftheMHV-1HEgenehav
6、egeneratedastretchofsequencewhichresembledthetranscriptionalinitiationmotif,andwasshowntoinitiatethesynthesisofanovelsmallermRNA.ThesefindingsstrengthenedthetheorythatinteractionsbetweenleaderRNAandtranscriptionalinitiationsequencesregulateMHVsubgenomicmRNAtra
7、nscrip-tion.SequenceanalysisrevealedthatmostMHVstrains,throughextensivemutations,deletions,orinsertions,havelostthecompleteHEopenreadingframe,thusturningHEintoapseudogene.Thishighdegreeofvariationisunusualastheotherthreestructuralproteins(spike,membrane,andnuc
8、leocapsid)arewell-maintained.Incontrasttobovinecoronavirus,whichapparentlyrequiresHEforviralreplication,theHEproteininMHVmaybeonlyanaccessorypro-teinwhichisnotnecessaryforviralrepl