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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Axl Receptor Tyrosine Kinase
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / metabolism*
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Cell Line
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Dendritic Cells / metabolism
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Dendritic Cells / virology
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Dystroglycans / genetics
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Dystroglycans / metabolism
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Humans
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Lassa Fever / genetics
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Lassa Fever / metabolism*
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Lassa Fever / virology
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Lassa virus / genetics
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Lassa virus / physiology*
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Lectins, C-Type / genetics
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Lectins, C-Type / metabolism*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor Protein-Tyrosine Kinases / metabolism*
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism*
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Receptors, Virus / genetics
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Receptors, Virus / metabolism*
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Virus Internalization*
Substances
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CLEC4G protein, human
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Cell Adhesion Molecules
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DC-specific ICAM-3 grabbing nonintegrin
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Lectins, C-Type
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Proto-Oncogene Proteins
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Receptors, Cell Surface
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Receptors, Virus
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Dystroglycans
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Receptor Protein-Tyrosine Kinases
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TYRO3 protein, human
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Axl Receptor Tyrosine Kinase