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1、SeminarsinVIROLOGY8,101–111(1997)ArticleNo.VI970109RecombinationandCoronavirusDefectiveInterferingRNAsDavidA.BrianandWillyJ.M.Spaan*DepartmentofMicrobiology,CollegeofVeterinaryMedicine,M409WaltersLifeSciencesBuilding,UniversityofTennessee,Knoxville,Tennessee37996-0845;and*DepartmentofVirology,Ins
2、tituteofMedicalMicrobiology,LeidenUniversity,2300RCLeiden,TheNetherlandsNaturallyoccurringdefectiveinterferingRNAshavebeenfoundin4of14coronavirusspecies.Theyrangeinsizefrom2.2kbtoapproximately25kb,or80%ofthe30-kbparentvirusgenome.ThelargeDIRNAsdonotinallcasesappeartorequirehelpervirusforintracell
3、ularreplicationandithasbeenpostulatedthattheymayontheirownfunctionasagentsofdisease.CoronavirusDIRNAsappeartoarisebyinternaldeletions(throughnonhomologousrecombinationevents)onthevirusgenomeoronDIRNAsoflargersizebyapolymerasestrand-switching(copy-choice)mechanism.Inadditiontotheiruseinthestudyofv
4、irusRNAreplicationandvirusassembly,coronavirusDIRNAsarebeingusedinamajorwaytostudythemechanismofahigh-frequency,site-specificRNArecombinationeventthatleadstoleaderacquisitionduringvirusreplication(i.e.,theleaderfusioneventthatoccursduringsynthesisofsubgenomicmRNAs,andtheleader-switchingeventthatca
5、noccurduringDIRNAreplication),adistinguishingfeatureofcoronaviruses(andarteriviruses).CoronavirusDIRNAsarealsobeingengineeredasvehiclesforthegenerationoftargetedrecombinantsoftheparentvirusgenome.r1997AcademicPressKEYWORDS:RNArecombination;leaderfusion;recombinantcoronaviruses.DISCUSSIONrearrange
6、dsequences(i.e.,nonlinearwiththeparentalvirusgenome)havebeenfoundinthegenomesofvirusrecombinants(10,11).IntheabsenceofevidenceRecombinationandtheOriginofCoronavirussupportingasplicingprocessincoronavirusRNADIRNAssynthesis(12±14),themostlikelymechanismfortheoriginofDIRNA,theonepresumedinthisreview
7、,NaturallyoccurringDIRNAshavebeenreportedappearstobetemplatestrandswitchingbytheRNAforthemousehepatitisvirus(MHV)(1±3),bovinepolymerasefromadonortemplatetoanacceptorcoronavirus(BCV)(4),porcinetransmissiblegastroen-temp
