Identification of cell surface molecules involved in dystroglycan-independent Lassa virus cell entry

Masayuki Shimojima; Ute Ströher; Hideki Ebihara; Heinz Feldmann; Yoshihiro Kawaoka

doi:10.1128/JVI.06451-11

Identification of cell surface molecules involved in dystroglycan-independent Lassa virus cell entry

J Virol. 2012 Feb;86(4):2067-78. doi: 10.1128/JVI.06451-11. Epub 2011 Dec 7.

Authors

Masayuki Shimojima¹, Ute Ströher, Hideki Ebihara, Heinz Feldmann, Yoshihiro Kawaoka

Affiliation

¹ Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. shimoji-@yamaguchi-u.ac.jp

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Axl Receptor Tyrosine Kinase
Cell Adhesion Molecules / genetics
Cell Adhesion Molecules / metabolism*
Cell Line
Dendritic Cells / metabolism
Dendritic Cells / virology
Dystroglycans / genetics
Dystroglycans / metabolism
Humans
Lassa Fever / genetics
Lassa Fever / metabolism*
Lassa Fever / virology
Lassa virus / genetics
Lassa virus / physiology*
Lectins, C-Type / genetics
Lectins, C-Type / metabolism*
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism*
Receptor Protein-Tyrosine Kinases / genetics
Receptor Protein-Tyrosine Kinases / metabolism*
Receptors, Cell Surface / genetics
Receptors, Cell Surface / metabolism*
Receptors, Virus / genetics
Receptors, Virus / metabolism*
Virus Internalization*

Substances

CLEC4G protein, human
Cell Adhesion Molecules
DC-specific ICAM-3 grabbing nonintegrin
Lectins, C-Type
Proto-Oncogene Proteins
Receptors, Cell Surface
Receptors, Virus
Dystroglycans
Receptor Protein-Tyrosine Kinases
TYRO3 protein, human
Axl Receptor Tyrosine Kinase