title: Sialic acid-dependent cell entry of human enterovirus D68.
abstract: Human enterovirus D68 (EV-D68) is a causative agent of childhood respiratory diseases and has now emerged as a global public health threat. Nevertheless, knowledge of the tissue tropism and pathogenesis of EV-D68 has been hindered by a lack of studies on the receptor-mediated EV-D68 entry into host cells. Here we demonstrate that cell surface sialic acid is essential for EV-D68 to bind to and infect susceptible cells. Crystal structures of EV-D68 in complex with sialylated glycan receptor analogues show that they bind into the 'canyon' on the virus surface. The sialic acid receptor induces a cascade of conformational changes in the virus to eject a fatty-acid-like molecule that regulates the stability of the virus. Thus, virus binding to a sialic acid receptor and to immunoglobulin-like receptors used by most other enteroviruses share a conserved mechanism for priming viral uncoating and facilitating cell entry.
authors.affiliation: Department of Biological Sciences, Hockmeyer Hall of Structural Biology, 240 South Martin Jischke Drive, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biological Sciences, Hockmeyer Hall of Structural Biology, 240 South Martin Jischke Drive, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Ju
authors.initials: J
authors.lastname: Sheng
authors.affiliation: Department of Infectious Diseases and Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, The Netherlands.
authors.forename: Jim
authors.initials: J
authors.lastname: Baggen
authors.affiliation: Department of Biological Sciences, Hockmeyer Hall of Structural Biology, 240 South Martin Jischke Drive, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Geng
authors.initials: G
authors.lastname: Meng
authors.affiliation: Department of Chemistry, University of Texas at El Paso, 500 W. University Avenue, El Paso, Texas 79968-0519, USA.
authors.forename: Chuan
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Department of Infectious Diseases and Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, The Netherlands.
authors.forename: Hendrik J
authors.initials: HJ
authors.lastname: Thibaut
authors.affiliation: Department of Infectious Diseases and Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, The Netherlands.
authors.forename: Frank J M
authors.initials: FJ
authors.lastname: van Kuppeveld
authors.affiliation: Department of Biological Sciences, Hockmeyer Hall of Structural Biology, 240 South Martin Jischke Drive, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rossmann
mesh_terms: D030016:Enterovirus D, Human / Q000235:genetics / Q000502:physiology*; D004769:Enterovirus Infections / Q000821:virology*; D006801:Humans; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D053586:Virus Internalization
chemical_list: D011956:Receptors, Cell Surface; D011991:Receptors, Virus; C092488:sialic acid receptor; D019158:N-Acetylneuraminic Acid