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Production of Human Norovirus Protruding Domains in E. coli for X-ray Crystallography
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Production of Human Norovirus Protruding Domains in E. coli for X-ray Crystallography

Published on: April 19, 2016

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Discovery of a proteinaceous cellular receptor for a norovirus

Robert C Orchard1, Craig B Wilen1, John G Doench2

  • 1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Science (New York, N.Y.)
|August 20, 2016
PubMed

Insights

Noroviruses (NoVs) are a major cause of gastroenteritis. Researchers found that CD300lf acts as a protein receptor essential for murine NoV (MNoV) infection, determining its host range.

Area of Science:

  • Virology
  • Immunology
  • Structural Biology

Background:

  • Noroviruses (NoVs) are a significant global cause of gastroenteritis.
  • Understanding the host factors enabling NoV infection is crucial for developing control strategies.

Purpose of the Study:

  • To identify host molecules essential for murine norovirus (MNoV) infection.
  • To elucidate the role of identified host factors in MNoV binding, replication, and species tropism.

Main Methods:

  • Cell-based assays to identify host factors involved in MNoV-induced cell death.
  • Genetic knockout of the identified host factor (Cd300lf) in mice.
  • Expression of human CD300lf in human cells to assess MNoV replication.
  • Crystallography to determine the structure of the CD300lf ectodomain.

Main Results:

  • CD300lf was identified as a proteinaceous receptor essential for MNoV binding and replication in cell lines and primary cells.
  • Cd300lf knockout mice exhibited resistance to MNoV infection.
  • Expression of human CD300lf enabled MNoV replication in human cells, breaking the species barrier.
  • Structural analysis revealed a ligand-binding cleft in CD300lf critical for MNoV infection.

Conclusions:

  • CD300lf is a key determinant of MNoV species tropism, acting as the primary protein receptor.
  • The cellular machinery for NoV replication is conserved between mice and humans, with the receptor being the main specificity factor.

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