Sequential control of hepatitis B virus in a mouse model of acute， self-resolving hepatitis B.pdf

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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、muneresponsetothewhenspecificandnonspecificTcellsinfiltratedtheliverandhumanhepatitisBvirus(HBV)arepoorlyunderstood.Asintrahepaticinterferonclevelspeakedaroundday7,butstudiesinmanandchimpanzeesarelimited,weaimedatreplicatedagainfromday10today24andpersisteda

5、tlowdevelopingamodelofself-limitinghepatitisBinmicethatlevelsthereafterdespitethepresenceofHBV-specificTcells.helpstodissectthecontrolofHBVbyhumoralandcellularFinally,HBVreplicationwasterminatedafterasufficientimmuneresponses.Adenoviralvectorscontaining1.3

6、-foldB-cellresponsehadbeenmounted–indicatedbyanti-HBsHBVgenomesallowedanefficientandreproducibletransferseroconversionaroundday35.HBV-specificTcellsinfil-ofHBVgenomesintomouseliversandinitiatedHBVrepli-tratedtheliverasecondtimearoundday70postinfection.catio

7、ninmice.HBVtranscriptsweredetectedinmouseThisdemonstratesthattheestablishedmousemodelallowsliversformorethan3months.HBsAgandHBeAgpeakedstudyingtheonsetandterminationofHBVinfectionandaroundday6andslowlydeclinedthereafter.Atwo-phasewillhelptodissectthedete

8、rminantsofHBVcontrolandmildtomoderateliverinflammationwithelevatedserumclearancebytheimmuneresponse.alanintransaminaseactivitieswasobservedaroundday7andaroundday70whenthevastmajorityofHBV-specificTKeywords:adenoviralvector,A