Rituximab Treatment in Hepatitis C Infection An In Vitro Model to Study the Impact of B Cell Depletion on Virus Infectivity 英文参考文献.docVIP

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Rituximab Treatment in Hepatitis C Infection An In Vitro Model to Study the Impact of B Cell Depletion on Virus Infectivity 英文参考文献.doc

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Rituximab Treatment in Hepatitis C Infection An In Vitro Model to Study the Impact of B Cell Depletion on Virus Infectivity 英文参考文献

RituximabTreatmentinHepatitisCInfection:AnInVitro ModeltoStudytheImpactofBCellDepletiononVirus Infectivity ZaniaStamataki1,2*,SamanthaTilakaratne1,DavidH.Adams1,2,JaneA.McKeating1 1MedicalResearchCouncilCentreforImmuneRegulation,UniversityofBirmingham,Birmingham,UnitedKingdom,2NationalInstituteforHealthResearchBiomedical ResearchUnitandCentreforLiverResearch,UniversityofBirmingham,Birmingham,UnitedKingdom Abstract Hepatitis C virus (HCV) infected patients with vasculitis are often treated with the B-cell-depleting anti-CD20 antibody rituximab.Treatmentreducesthecryoglobulinsthatcausevasculitis,yetitalsoleadstoatransientincreaseinliverenzymes andHCVgenomicRNAintheperiphery.Themechanismunderlyingtheincreasedviralloadisunclearandbothdirectand indirectroleshavebeenproposedforBcellsinHCVinfection.WepreviouslyreportedthatHCVcanassociatewithBcells andcantrans-infecthepatocytes.Weestablishedaninvitroassaytostudytheeffect(s)ofrituximabonBcell-associatedHCV infectivity.Rituximab-mediatedlysisofBcellsinvitroincreasesthelevelofinfectiousHCVreleasedfromBcells.Ourresults, usingamodelwherevirusdoesnotreplicateinBcells,recapitulateobservationsseeninpatientsandmayexplaininpart therapidincreaseinbloodHCVRNAobservedafterrituximabtreatment. Citation:StamatakiZ,TilakaratneS,AdamsDH,McKeatingJA(2011)RituximabTreatmentinHepatitisCInfection:AnInVitroModeltoStudytheImpactofBCell DepletiononVirusInfectivity.PLoSONE6(9):e25789.doi:10.1371/journal.pone.0025789 Editor:JianmingQiu,UniversityofKansasMedicalCenter,UnitedStatesofAmerica ReceivedJuly16,2011;AcceptedSeptember10,2011;PublishedSeptember30,2011 Copyright: ? 2011 Stamataki et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: This work was supported by grants from the Medical Research Council, United Kingdom (no. G0400802). ZS is currently funded by a Rese