Effect of combined siRNA of HCV E2 gene and HCV receptors against HCV.docVIP

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Effect of combined siRNA of HCV E2 gene and HCV receptors against HCV.doc

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Effect of combined siRNA of HCV E2 gene and HCV receptors against HCV

Jahanetal.VirologyJournal2011,8:295 /content/8/1/295 RESEARCH OpenAccess EffectofcombinedsiRNAofHCVE2geneand HCVreceptorsagainstHCV ShahJahan1*?,SabaKhaliq1*?,BailaSamreen ,BushraIjaz ,MahwishKhan ,WaqarAhmad ,UsmanAlliAAshfaq2 1? 1 1 1 andSajidaHassan1 Abstract Background/Aim:HepatitisCvirus(HCV)isamajorthreatasalmost3%oftheworld’spopulation(350million individual)and10%ofthePakistanipopulationischronicallyinfectedwiththisvirus.RNAinterference(RNAi),a sequence-specificdegradationprocessofRNA,haspotentialtobeusedasapowerfulalternativemolecular therapeuticapproachinspiteofthecurrenttherapyofinterferon-aandribavirinagainstHCVwhichhaslimited efficiency.HCVstructuralgeneE2ismainlyinvolvedinviralcellentryviaattachmentwiththehostcellsurface receptorsi.e.,CD81tetraspanin,lowdensitylipoproteinreceptor(LDLR),scavengerreceptorclassBtype1(SR-B1), andClaudin1(CLDN1).ConsideringtheimportanceofHCVE2geneandcellularreceptorsinvirusinfectionand silencingeffectsofRNAi,thecurrentstudywasdesignedtotargetthecellularandviralfactorsasnewtherapeutic optionsinlimitingHCVinfection. Results:InthisstudythepotentialofsiRNAstoinhibitHCV-3areplicationinserum-infectedHuh-7cellswas investigatedbycombinedtreatmentofsiRNAsagainsttheHCVE2geneandHCVcellularreceptors(CD81and LDLR),whichresultedinasignificantdecreaseinHCVviralcopynumber. Conclusion:FromthecurrentstudyitisconcludedthatthecombinedRNAi-mediatedsilencingofHCVE2and HCVreceptorsisimportantforthedevelopmentofeffectivesiRNA-basedtherapeuticoptionagainstHCV-3a. Keywords:HCV,siRNA,HCVreceptors,HCVenvelopegenesandviraltiter Introduction HCV infection is a major health problem with nearly 10%chronicallyinfectedpopulationinPakistanand350 better therapeutic alternative for treatment of HCV infections. Duetotheabsenceofsuitableanimalmodelandcom- million people worldwide [1,2]. About 75% of patients petentinvitrocellculturesystemthemechanismofHCV achievenotherapeuticbenefitfromthepresentcombi- cellentrywasunrevealedafteralongtime.Recently,di