Assessment of the Antiviral Properties of Recombinant Porcine SP-D against Various Influenza A Viruses In Vitro 英文参考文献.docVIP

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Assessment of the Antiviral Properties of Recombinant Porcine SP-D against Various Influenza A Viruses In Vitro 英文参考文献.doc

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Assessment of the Antiviral Properties of Recombinant Porcine SP-D against Various Influenza A Viruses In Vitro 英文参考文献

AssessmentoftheAntiviralPropertiesofRecombinant PorcineSP-DagainstVariousInfluenzaAVirusesInVitro MarineL.B.Hillaire1,MartinvanEijk2,StellaE.vanTrierum1,DebbyvanRiel1,XavierSaelens3,4, RolandA.Romijn5,WiegerHemrika5,RonA.M.Fouchier1,ThijsKuiken1,AlbertD.M.E.Osterhaus1,6, HenkP.Haagsman2*,GuusF.Rimmelzwaan1,6* 1ErasmusMedicalCentre,Rotterdam,TheNetherlands,2DepartmentofInfectiousDiseasesandImmunology,FacultyofVeterinaryMedicine,UtrechtUniversity,Utrecht, TheNetherlands,3DepartmentforMolecularBiomedicalResearch,VIB,Ghent,Belgium,4DepartmentofBiomedicalMolecularBiology,GhentUniversity,Ghent,Belgium, 5U-ProteinExpressB.V.,ScienceParkUtrecht,Utrecht,TheNetherlands,6ViroclinicsBiosciencesBV,Rotterdam,TheNetherlands Abstract Theemergenceofinfluenzavirusesresistanttoexistingclassesofantiviraldrugsraisesconcernandthereisaneedfornovel antiviralagentsthatcouldbeusedtherapeuticallyorprophylacticaly.SurfactantproteinD(SP-D)belongstothefamilyofC- typelectinswhichareimportanteffectormoleculesoftheinnateimmunesystemwithactivityagainstbacteriaandviruses, including influenza viruses. In the present study we evaluated the potential of recombinant porcine SP-D as an antiviral agentagainstinfluenzaAviruses(IAVs)invitro.Todeterminetherangeofantiviralactivity,thirtyIAVsofthesubtypesH1N1, H3N2andH5N1thatoriginatedfrombirds,pigsandhumanswereselectedandtestedfortheirsensitivitytorecombinant SP-D. Using these viruses it was shown by hemagglutination inhibition assay, that recombinant porcine SP-D was more potentthanrecombinanthumanSP-DandthatespeciallyhigherorderoligomericformsofSP-Dhadthestrongestantiviral activity. Porcine SP-D was active against abroad range of IAV strains and neutralized a variety of H1N1 and H3N2IAVs, including 2009 pandemic H1N1 viruses. Using tissue sections of ferret and human trachea, we demonstrated that recombinantporcineSP-DpreventedattachmentofhumanseasonalH1N1andH3N2virustoreceptorsonepithelialcellsof theupperrespiratorytract.Itwasconcludedthatrecombinantporci