Focal Distribution of Hepatitis C Virus RNA in Infected Livers 英文参考文献.docVIP

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Focal Distribution of Hepatitis C Virus RNA in Infected Livers 英文参考文献.doc

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FocalDistributionofHepatitisCVirusRNAinInfected Livers J.DavidStiffler1,MinhhuyenNguyen1,JiA.Sohn1,ChenLiu2,DavidKaplan3,4,ChristophSeeger1* 1FoxChaseCancerCenter,Philadelphia,Pennsylvania,UnitedStatesofAmerica,2UniversityofFlorida,Gainesville,Florida,UnitedStatesofAmerica,3ResearchSection, Philadelphia Veterans Administration Medical Center, Philadelphia, Pennsylvania, United States of America, 4Gastroenterology Division, University of Pennsylvania, Philadelphia,Pennsylvania,UnitedStatesofAmerica Abstract Background:HepatitisCvirus(HCV)isaplus-strandRNAvirusthatreplicatesbyamplificationofgenomicRNAfromminus strandsleadingtoaccumulationofalmostonethousandcopiespercellunderinvitrocellcultureconditions.Incontrast, HCVRNAcopynumbersinliversofinfectedpatientsappeartobemuchlower,estimatedatafewcopiespercell. Methodology/PrincipalFindings:TogaininsightsintomechanismsthatcontrolHCVreplicationinvivo,weanalyzedHCV RNAlevelsaswellasexpressionofinterferonbeta(IFNb)andseveralinterferonstimulatedgenes(ISGs)fromwholeliver sectionsandmicro-dissectedsubpopulationsofhepatocytesinbiopsysamplesfrom21HCV-infectedpatients.Theresults showedthatintrahepaticHCVRNAlevelsrangeformlessthanonecopyperhepatocytetoamaximumofabouteight.A correlation existed between viral RNA levels and IFNb expression, but not between viral RNA and ISG levels. Also, IFNb expressiondidnotcorrelatewithISGslevels.ReplicationofHCVRNAoccurredinfocalareasintheliverinthepresenceofa generalinductionofISGs. Conclusion/Significance:ThelowaveragelevelsofHCVRNAinbiopsysamplescanbeexplainedbyfocaldistributionof infectedhepatocytes.HCVreplicationdirectlyinducesIFNb,whichthenactivatesISGs.Theapparentlackofacorrelation between levels of IFNb and ISG expression indicates that control of the innate immune response during HCV infections dependsonmultiplefactors. Citation: Stiffler JD, Nguyen M, Sohn JA, Liu C, Kaplan D, et al. (2009) Focal Distribution of Hepatitis C Virus RNA in Infected Livers. PLoS ONE 4(8): e6661. doi:10.1371/jo