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Effects of Interferon-αβ on HBV Replication Determined by Viral Load 英文参考文献
EffectsofInterferon-a/bonHBVReplicationDetermined
byViralLoad
YongjunTian,Wen-lingChen,Jing-hsiungJamesOu*
DepartmentofMolecularMicrobiologyandImmunology,KeckSchoolofMedicine,UniversityofSouthernCalifornia,LosAngeles,California,UnitedStatesofAmerica
Abstract
Interferonsaandb(IFN-a/b)aretypeIinterferonsproducedbythehosttocontrolmicrobialinfections.However,theuseof
IFN-atotreathepatitisBvirus(HBV)patientsgeneratedsustainedresponsetoonlyaminorityofpatients.ByusingHBV
transgenicmiceasamodelandbyusinghydrodynamicinjectiontointroduceHBVDNAintothemouseliver,westudied
theeffectofIFN-a/bonHBVinvivo.Interestingly,ourresultsindicatedthatIFN-a/bcouldhaveoppositeeffectsonHBV:
theysuppressedHBVreplicationwhenviralloadwashighandenhancedHBVreplicationwhenviralloadwaslow.IFN-a/b
apparently suppressed HBV replication via transcriptional and post-transcriptional regulations. In contrast, IFN-a/b
enhancedviralreplicationbyinducingthetranscriptionfactorHNF3candactivatingSTAT3,whichtogetherstimulatedHBV
gene expression and replication. Further studies revealed an important role of IFN-a/b in stimulating viral growth and
prolongingviremiawhenviralloadislow.Thisuseofaninnateimmuneresponsetoenhanceitsreplicationandpersistence
mayrepresentanovelstrategythatHBVusestoenhanceitsgrowthandspreadintheearlystageofviralinfectionwhenthe
virallevelislow.
Citation: Tian Y, Chen W-l, Ou J-hJ (2011) Effects of Interferon-a/b on HBV Replication Determined by Viral Load. PLoS Pathog 7(7): e1002159. doi:10.1371/
journal.ppat.1002159
Editor:ChristopherM.Walker,NationwideChildren’sHospital,UnitedStatesofAmerica
ReceivedJanuary26,2011;AcceptedMay25,2011;PublishedJuly28,2011
Copyright:?2011Tianetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted
use,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited.
Funding:ThisresearchissupportedbyNIHgrantsCA123328andAI083025.Thefunderhadnoroleinstudydesign,datacollectionandan
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