Discovery of a proteinaceous cellular receptor for a norovirus.

Science
Authors
Abstract

Noroviruses (NoVs) are a leading cause of gastroenteritis globally, yet the host factors required for NoV infection are poorly understood. We identified host molecules that are essential for murine NoV (MNoV)-induced cell death, including CD300lf as a proteinaceous receptor. We found that CD300lf is essential for MNoV binding and replication in cell lines and primary cells. Additionally, Cd300lf(-/-) mice are resistant to MNoV infection. Expression of CD300lf in human cells breaks the species barrier that would otherwise restrict MNoV replication. The crystal structure of the CD300lf ectodomain reveals a potential ligand-binding cleft composed of residues that are critical for MNoV infection. Therefore, the presence of a proteinaceous receptor is the primary determinant of MNoV species tropism, whereas other components of cellular machinery required for NoV replication are conserved between humans and mice.

Year of Publication
2016
Journal
Science
Volume
353
Issue
6302
Pages
933-6
Date Published
2016 08 26
ISSN
1095-9203
DOI
10.1126/science.aaf1220
PubMed ID
27540007
Links
Grant list
U19 AI109725 / AI / NIAID NIH HHS / United States
P30 CA091842 / CA / NCI NIH HHS / United States
F31 CA177194 / CA / NCI NIH HHS / United States
T32 CA009547 / CA / NCI NIH HHS / United States