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1、JournalofViralHepatitis,2011,18,216–226doi:10.1111/j.1365-2893.2010.01302.xSequentialcontrolofhepatitisBvirusinamousemodelofacute,self-resolvinghepatitisB11234M.JohnvonFreyend,A.Untergasser,S.Arzberger,H.Oberwinkler,U.Drebber,P.Schirmacher5andU.Protzer2,
2、61InstituteforMedicalMicrobiology,ImmunologyandHygieneandCenterforMolecularMedicine23Cologne,UniversityofCologne;InstituteofVirology,TechnischeUniversita¨tMu¨nchen/HelmholtzZentrumMu¨nchen,Munich;Departmentof45Virology,UniversityofHeidelberg,Heidelberg;D
3、epartmentofPathology,UniversityHospitalCologne,CologneandInstituteofPathology,University6ofHeidelberg,Heidelberg;andImmuneMonitoring,HelmholtzZentrumMu¨nchen,Munich,GermanyReceivedOctober2009;acceptedforpublicationJanuary2010SUMMARY.Thedeterminantsofanim
4、muneresponsetothewhenspeci?candnonspeci?cTcellsin?ltratedtheliverandhumanhepatitisBvirus(HBV)arepoorlyunderstood.Asintrahepaticinterferonclevelspeakedaroundday7,butstudiesinmanandchimpanzeesarelimited,weaimedatreplicatedagainfromday10today24andpersisteda
5、tlowdevelopingamodelofself-limitinghepatitisBinmicethatlevelsthereafterdespitethepresenceofHBV-speci?cTcells.helpstodissectthecontrolofHBVbyhumoralandcellularFinally,HBVreplicationwasterminatedafterasuf?cientimmuneresponses.Adenoviralvectorscontaining1.3
6、-foldB-cellresponsehadbeenmounted–indicatedbyanti-HBsHBVgenomesallowedanef?cientandreproducibletransferseroconversionaroundday35.HBV-speci?cTcellsin?l-ofHBVgenomesintomouseliversandinitiatedHBVrepli-tratedtheliverasecondtimearoundday70postinfection.catio
7、ninmice.HBVtranscriptsweredetectedinmouseThisdemonstratesthattheestablishedmousemodelallowsliversformorethan3months.HBsAgandHBeAgpeakedstudyingtheonsetandterminationofHBVinfectionandaroundday6andslowlydeclinedthereafter.Atwo-phasewillhelptodissectthedete
8、rminantsofHBVcontrolandmildtomoderateliverin?ammationwithelevatedserumclearancebytheimmuneresponse.alanintransaminaseactivitieswasobservedaroundday7andaroundday70whenthevastmajorityofHBV-speci?cTKeywords:adenoviralvector,A
