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1、ArchVirol(2005)150:120DOI10.1007/s00705-004-0413-9TestingthehypothesisofarecombinantoriginoftheSARS-associatedcoronavirusX.W.Zhang1,Y.L.Yap1,andA.Danchin21HKU-PasteurResearchCentre,HongKong,P.R.China2PasteurInstitute,UnitGeneticsofBacterialGenomes,Paris,
2、FranceReceivedFebruary27,2004;acceptedAugust16,2004PublishedonlineOctober11,2004cSpringer-Verlag2004Summary.Theoriginofsevereacuterespiratorysyndrome-associatedcorona-virus(SARS-CoV)isstillamatterofspeculation,althoughmorethanoneyearhaspassedsincetheons
3、etoftheSARSoutbreak.Inthisstudy,weim-plementeda3-stepstrategytotesttheintriguinghypothesisthatSARS-CoVmighthavebeenderivedfromarecombinantvirus.First,weblastedthewholeSARS-CoVgenomeagainstavirusdatabasetosearchvirusesofinterest.Second,weemployed7recombin
4、ationdetectiontechniqueswelldocumentedinsuccess-fullydetectingrecombinationeventstoexplorethepresenceofrecombinationinSARS-CoVgenome.Finally,weconductedphylogeneticanalysestofurtherexplorewhetherrecombinationhasindeedoccurredinthecourseofcoronaviruseshis
5、torypredatingtheemergenceofSARS-CoV.Surprisingly,wefoundthat7putativerecombinationregions,locatedinReplicase1abandSpikeprotein,ex-istbetweenSARS-CoVandother6coronaviruses:porcineepidemicdiarrheavirus(PEDV),transmissiblegastroenteritisvirus(TGEV),bovineco
6、ronavirus(BCoV),humancoronavirus229E(HCoV),murinehepatitisvirus(MHV),andavianinfectiousbronchitisvirus(IBV).Thus,ouranalysessubstantiatethepres-enceofrecombinationeventsinhistorythatledtotheSARS-CoVgenome.Liketheothercoronavirusesusedintheanalysis,SARS-C
7、oVisalsoamosaicstructure.IntroductionSARS,anewdiseasecharacterizedbyhighfever,malaise,rigor,headacheandnon-productivecough,hasspreadtoover30countrieswitharound8%ofmor-talityrateonaverage.SequenceanalysisofSARScoronavirus(SARS-CoV)[17,25]showedthatitisano
8、velcoronavirus[12].Anandetal.[1]reportedathree-dimensionalmodelofSARS-CoVmainproteinaseandsuggestedthat2X.W.Zhangetal.modifiedrhinovirus3CproinhibitorscouldbeusefulforSARStherapy.Lipsitchetal.[15]developedamathematicalmodel