Secreted NS1 of Dengue Virus Attaches to the Surface of Cells via Interactions with Heparan Sulfate and Chondroitin Sulfate E 英文参考文献.docVIP

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Secreted NS1 of Dengue Virus Attaches to the Surface of Cells via Interactions with Heparan Sulfate and Chondroitin Sulfate E 英文参考文献.doc

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Secreted NS1 of Dengue Virus Attaches to the Surface of Cells via Interactions with Heparan Sulfate and Chondroitin Sulfate E 英文参考文献

SecretedNS1ofDengueVirusAttaches totheSurfaceofCellsviaInteractionswith HeparanSulfateandChondroitinSulfateE Panisadee Avirutnan1,2,Lijuan Zhang3,Nuntaya Punyadee2,Ananya Manuyakorn4,Chunya Puttikhunt5, Watchara Kasinrerk5,6,Prida Malasit5,John P.Atkinson1,3,7,Michael S.Diamond1,3,7* 1DepartmentofMedicine,WashingtonUniversitySchoolofMedicine,St.Louis,Missouri,UnitedStatesofAmerica,2MedicalMolecularBiologyUnit,OfficeforResearchand Development,MahidolUniversity,Bangkok,Thailand,3DepartmentofPathologyandImmunology,WashingtonUniversitySchoolofMedicine,St.Louis,Missouri,United StatesofAmerica,4DepartmentofPathology,FacultyofMedicineSirirajHospital,MahidolUniversity,Bangkok,Thailand,5MedicalBiotechnologyUnit,NationalCenterfor Genetic Engineering and Biotechnology BIOTEC, National Science and Technology Development Agency NSTDA, Pathumthani, Thailand, 6 Department of Medical Technology,FacultyofAssociatedMedicalSciences,ChiangMaiUniversity,ChiangMai,Thailand,7DepartmentofMolecularMicrobiology,WashingtonUniversitySchoolof Medicine,St.Louis,Missouri,UnitedStatesofAmerica Dengue virus (DENV) nonstructural protein-1 (NS1) is a secreted glycoprotein that is absent from viral particles but accumulates in the supernatant and on the plasma membrane of cells during infection. Immune recognition of cell surfaceNS1onendothelialcellshasbeenhypothesizedasamechanismforthevascularleakagethatoccursduring severeDENVinfection.However,ithasremainedunclearhowNS1becomesassociatedwiththeplasmamembrane,as itcontainsnomembrane-spanningsequencemotif.UsingflowcytometricandELISA-basedbindingassaysandmutant celllineslackingselectiveglycosaminoglycans,weshowthatsolubleNS1bindsbacktothesurfaceofuninfectedcells primarily via interactions with heparan sulfate and chondroitin sulfate E. DENV NS1 binds directly to the surface of manytypesofepithelialandmesenchymalcellsyetattachespoorlytomostperipheralbloodcells.Moreover,DENV NS1preferentiallybindstoculturedhumanmicrovascularcomparedtoaorticorumbilical