Effective Treatment of Respiratory Alphaherpesvirus Infection Using RNA Interference 英文参考文献.docVIP

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Effective Treatment of Respiratory Alphaherpesvirus Infection Using RNA Interference 英文参考文献.doc

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Effective Treatment of Respiratory Alphaherpesvirus Infection Using RNA Interference 英文参考文献

EffectiveTreatmentofRespiratoryAlphaherpesvirus InfectionUsingRNAInterference AmyFulton1,SarahT.Peters1,GillianA.Perkins2,KeithW.Jarosinski1,ArmandoDamiani1 ,Margaret Brosnahan1,ElizabethL.Buckles3,NikolausOsterrieder1,4*,GerlindeR.VandeWalle1 1DepartmentofMicrobiologyandImmunology,CollegeofVeterinaryMedicine,CornellUniversity,Ithaca,NewYork,UnitedStatesofAmerica,2DepartmentofClinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America, 3Department of Biomedical Sciences, College of Veterinary Medicine,CornellUniversity,Ithaca,NewYork,UnitedStatesofAmerica,4Institutfu¨rVirologie,FreieUniversita¨t Berlin,Berlin,Germany Abstract Background: Equine herpesvirus type 1 (EHV-1), a member of the Alphaherpesvirinae, is spread via nasal secretions and causesrespiratorydisease,neurologicaldisordersandabortions.Thevirusisasignificantequinepathogen,butcurrentEHV- 1 vaccines are only partially protective and effective metaphylactic and therapeutic agents are not available. Small interferingRNAs(siRNA’s),deliveredintranasally,couldproveavaluablealternativeforinfectioncontrol.siRNA’sagainsttwo essentialEHV-1genes,encodingtheviralhelicase(Ori)andglycoproteinB,wereevaluatedfortheirpotentialtodecrease EHV-1infectioninamousemodel. Methodology/PrincipalFndings:siRNAtherapyinvitrosignificantlyreducedvirusproductionandplaquesize.Viraltiters were reduced 80-fold with 37.5pmol of a single siRNA or with as little as 6.25pmol of each siRNA when used in combination. siRNA therapy in vivo significantly reduced viral replication and clinical signs. Intranasal treatment did not requireatransportvehicleandprovedeffectivewhengivenupto12hbeforeorafterinfection. Conclusions/Significance:siRNAtreatmenthaspotentialforbothpreventionandearlytreatmentofEHV-1infections. Citation: Fulton A, Peters ST, Perkins GA, Jarosinski KW, Damiani A, et al. (2009) Effective Treatment of Respiratory Alphaherpesvirus Infection Using RNA Interference.PLoSONE4(1