Adenovirus Delivered Short Hairpin RNA Targeting a Conserved Site in the 5′ Non-Translated Region Inhibits All Four Serotypes of Dengue Viruses 英文参考文献.docVIP

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Adenovirus Delivered Short Hairpin RNA Targeting a Conserved Site in the 5′ Non-Translated Region Inhibits All Four Serotypes of Dengue Viruses 英文参考文献.doc

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Adenovirus Delivered Short Hairpin RNA Targeting a Conserved Site in the 5′ Non-Translated Region Inhibits All Four Serotypes of Dengue Viruses 英文参考文献

AdenovirusDeliveredShortHairpinRNATargetinga ConservedSiteinthe59Non-TranslatedRegionInhibits AllFourSerotypesofDengueViruses AnilBabuKorrapati,GokulSwaminathan,AartiSingh,NavinKhanna,SathyamangalamSwaminathan* RecombinantGeneProductsGroup,InternationalCentreforGeneticEngineeringandBiotechnology,NewDelhi,India Abstract Background:Dengueisamosquito-borneviraldiseasecausedbyfourcloselyrelatedserotypesofDengueviruses(DENVs). This disease whose symptoms range from mild fever to potentially fatal haemorrhagic fever and hypovolemic shock, threatensnearlyhalftheglobalpopulation.Thereisneitherapreventivevaccinenoraneffectiveantiviraltherapyagainst denguedisease.Thedifferencebetweensevereandmilddiseaseappearstobedependentontheviralload.Earlydiagnosis mayenabletimelytherapeuticinterventiontobluntdiseaseseveritybyreducingtheviralload.Harnessingthetherapeutic potentialofRNAinterference(RNAi)toattenuateDENVreplicationmayofferoneapproachtodenguetherapy. Methodology/PrincipalFindings:Wescreenedthenon-translatedregions(NTRs)oftheRNAgenomesofrepresentative members of the four DENV serotypes for putative siRNA targets mapping to known transcription/translation regulatory elements.Weidentifiedatargetsiteinthe59NTRthatmapstothe59upstreamAUGregion,ahighlyconservedcis-acting elementessentialforviralreplication.Weusedareplication-defectivehumanadenovirustype5(AdV5)vectortodelivera short-hairpinRNA(shRNA)targetingthissiteintocells.WeshowthatthisshRNAmaturestothecognatesiRNAandisable toinhibiteffectivelyantigensecretion,viralRNAreplicationandinfectiousvirusproductionbyallfourDENVserotypes. Conclusion/Significance: The data demonstrate the feasibility of using AdV5-mediated delivery of shRNAs targeting conservedsitesintheviralgenometoachieveinhibitionofallfourDENVserotypes.Thispavesthewaytowardsexploration ofRNAiasapossibletherapeuticstrategytocurtailDENVinfection. Citation:KorrapatiAB,SwaminathanG,SinghA,KhannaN,SwaminathanS(2012)AdenovirusDeliveredShortHairpinRNATargetingaConservedSitein