title: Enterovirus 70 binds to different glycoconjugates containing alpha2,3-linked sialic acid on different cell lines.
abstract: Enterovirus 70 (EV70), the causative agent of acute hemorrhagic conjunctivitis, exhibits a restricted tropism for conjunctival and corneal cells in vivo but infects a wide spectrum of mammalian cells in culture. Previously, we demonstrated that human CD55 is a receptor for EV70 on HeLa cells but that EV70 also binds to sialic acid-containing receptors on a variety of other human cell lines. Virus recognition of sialic acid attached to underlying glycans by a particular glycosidic linkage may contribute to host range, tissue tropism, and pathogenesis. Therefore, we tested the possibility that EV70 binds to alpha2,3-linked sialic acid, like other viruses associated with ocular infections. Through the use of linkage-specific sialidases, sialyltransferases, and lectins, we show that EV70 recognizes alpha2,3-linked sialic acid on human corneal epithelial cells and on U-937 cells. Virus attachment to both cell lines is CD55 independent and sensitive to benzyl N-acetyl-alpha-D-galactosaminide, an inhibitor of O-linked glycosylation. Virus binding to corneal cells, but not U-937 cells, is inhibited by proteinase K, but not by phosphatidylinositol-specific phospholipase C treatment. These results are consistent with the idea that a major EV70 receptor on corneal epithelial cells is an O-glycosylated, non-glycosyl phosphatidylinositol-anchored membrane glycoprotein containing alpha2,3-linked sialic acid, while sialylated receptors on U-937 cells are not proteinaceous.
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Rd., Ottawa, ON, Canada K1H 8M5.
authors.forename: M Reza
authors.initials: MR
authors.lastname: Nokhbeh
authors.forename: Samir
authors.initials: S
authors.lastname: Hazra
authors.forename: David A
authors.initials: DA
authors.lastname: Alexander
authors.forename: Ahmar
authors.initials: A
authors.lastname: Khan
authors.forename: Morgan
authors.initials: M
authors.lastname: McAllister
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Suuronen
authors.forename: May
authors.initials: M
authors.lastname: Griffith
authors.forename: Kenneth
authors.initials: K
authors.lastname: Dimock
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D003232:Conjunctivitis, Acute Hemorrhagic / Q000209:etiology; D003315:Cornea / Q000378:metabolism / Q000821:virology; D030016:Enterovirus D, Human / Q000472:pathogenicity* / Q000502:physiology*; D004769:Enterovirus Infections / Q000209:etiology; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D006001:Glycoconjugates / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008253:Macaca mulatta; D009439:Neuraminidase / Q000494:pharmacology; D011991:Receptors, Virus / Q000737:chemistry / Q000502:physiology*; D012794:Sialic Acids / Q000737:chemistry; D012799:Sialyltransferases / Q000494:pharmacology; D020298:U937 Cells; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
chemical_list: D006001:Glycoconjugates; D037102:Lectins; D011991:Receptors, Virus; D012794:Sialic Acids; D012799:Sialyltransferases; D009439:Neuraminidase; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase