title: Identification of cell surface molecules involved in dystroglycan-independent Lassa virus cell entry.
abstract: Although O-mannosylated dystroglycan is a receptor for Lassa virus, a causative agent of Lassa fever, recent findings suggest the existence of an alternative receptor(s). Here we identified four molecules as receptors for Lassa virus: Axl and Tyro3, from the TAM family, and dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) and liver and lymph node sinusoidal endothelial calcium-dependent lectin (LSECtin), from the C-type lectin family. These molecules enhanced the binding of Lassa virus to cells and mediated infection independently of dystroglycan. Axl- or Tyro3-mediated infection required intracellular signaling via the tyrosine kinase activity of Axl or Tyro3, whereas DC-SIGN- or LSECtin-mediated infection and binding were dependent on a specific carbohydrate and on ions. The identification of these four molecules as Lassa virus receptors advances our understanding of Lassa virus cell entry.
authors.affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. shimoji-@yamaguchi-u.ac.jp
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shimojima
authors.forename: Ute
authors.initials: U
authors.lastname: Ströher
authors.forename: Hideki
authors.initials: H
authors.lastname: Ebihara
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003713:Dendritic Cells / Q000378:metabolism / Q000821:virology; D049030:Dystroglycans / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007835:Lassa Fever / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D007836:Lassa virus / Q000235:genetics / Q000502:physiology*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization; D000094963:Axl Receptor Tyrosine Kinase; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D049030:Dystroglycans; D037181:Lectins, C-Type; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D000094963:Axl Receptor Tyrosine Kinase; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C505228:CLEC4G protein, human; C084944:TYRO3 protein, human