Elucidating the Mechanisms of Influenza Virus Recognition by Ncr1 英文参考文献.docVIP

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Elucidating the Mechanisms of Influenza Virus Recognition by Ncr1 英文参考文献.doc

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Elucidating the Mechanisms of Influenza Virus Recognition by Ncr1 英文参考文献

ElucidatingtheMechanismsofInfluenzaVirus RecognitionbyNcr1 AriellaGlasner1,AntonijaZurunic2,TalMeningher3,TihanaLenacRovis2,PinchasTsukerman1, YotamBar-On1,RachelYamin1,AdrienneF.A.Meyers4,MichalMandeboim5,StipanJonjic2, OferMandelboim1* 1The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel Canada (IMRIC). Hebrew University-Hadassah Medical School, Jerusalem,Israel,2DepartmentofHistologyandEmbryology/CenterforProteomics,FacultyofMedicine,UniversityofRijeka,Rijeka,Croatia,3FacultyofLifeSciences, Bar-Ilan University, Ramat Gan, Israel, 4National Laboratory for HIV Viral Immunology National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Winnipeg,Manitoba,Canada,5CentralVirologyLaboratory,MinistryofHealth,ChaimShebaMedicalCenter,Ramat-Gan,Israel Abstract Naturalkiller(NK)cellsareinnatecytotoxiclymphocytesthatspecializeinthedefenseagainstviralinfectionandoncogenic transformation.Theiractionistightlyregulatedbysignalsderivedfrominhibitoryandactivatingreceptors;thelaterinclude proteinssuchastheNaturalCytotoxicityReceptors(NCRs:NKp46,NKp44andNKp30).AmongtheNCRs,NKp46istheonly receptorthathasamouseorthologuenamedNcr1.NKp46/Ncr1isalsoauniquemarkerexpressedonNKandonLymphoid tissue inducer (LTI) cells and it was implicated in the control of various viral infections, cancer and diabetes. We have previouslyshownthathumanNKp46recognizesviralhemagglutinin(HA)inasialicacid-dependentmannerandthattheO- glycosylationisessentialfortheNKp46bindingtoviralHA.HerewestudiedthemolecularinteractionsbetweenNcr1and influenzaviruses.WeshowthatNcr1recognizesinfluenzavirusinasialicaciddependentmannerandthatN-glycosylation isimportantforthisbinding.SurprisinglywedemonstratethatnoneofthepredictedN-glycosilatedresiduesofNcr1are essential for its binding to influenza virus and we thus conclude that other, yet unidentified N-glycosilated residues are responsibleforitsrecognition.WehavedemonstratedthatNglycosylationplaylittleroleintherecogni