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.

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

  • 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