Discovery of a proteinaceous cellular receptor for a norovirus
SCIENCE
Authors: Orchard, Robert C.; Wilen, Craig B.; Doench, John G.; Baldridge, Megan T.; McCune, Broc T.; Lee, Ying-Chiang J.; Lee, Sanghyun; Pruett-Miller, Shondra M.; Nelson, Christopher A.; Fremont, Daved H.; Virgin, Herbert W.
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.
Open Sesame: New Keys to Unlocking the Gate to Norovirus Infection
CELL HOST & MICROBE
Authors: Lingemann, Marit; Taube, Stefan
Abstract
Three recent papers highlight the impact of an entry receptor on murine norovirus pathogenesis. CD300lf was shown to be the first proteinaceous entry receptor for a norovirus, specialized intestinal epithelial cells constitute the reservoir for persistence, and a new link between the receptor and a lipid biosynthetic enzyme was revealed.