@article{0c8ca3705302478cab09bd5f8fb86493,
title = "Discovery of a proteinaceous cellular receptor for a norovirus",
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.",
author = "Orchard, {Robert C.} and Wilen, {Craig B.} and Doench, {John G.} and Baldridge, {Megan T.} and McCune, {Broc T.} and Lee, {Ying Chiang J.} and Sanghyun Lee and Pruett-Miller, {Shondra M.} and Nelson, {Christopher A.} and Fremont, {Daved H.} and Skip Virgin",
note = "Funding Information: We thank S. Karst and M. Diamond for providing valuable reagents and S. Handley and C. Desai for their helpful discussion and figure generation. We thank the Alvin J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, Missouri, for the use of the Genome Engineering and iPSC Center. CD300 constructs, cell lines, and mice are available from H.W.V. under a material transfer agreement with Washington University. The data from this study are tabulated in the main paper and in the supplementary materials. H.W.V., D.H.F., R.C.O., C.B.W., and C.A.N. are inventors on a patent application submitted by Washington University entitled {"}Receptor for norovirus and uses thereof{"} (U.S. Provisional Application 62/301, 965). The atomic coordinates are deposited in the Protein Data Bank under accession code 5FFL. The Siteman Cancer Center is supported in part by National Cancer Institute Cancer Center Support Grant P30 CA091842. This work was supported by NIH grants U19 AI109725 (H.W.V.), 1F31CA177194 (B.T.M.), and 5T32CA009547 (M.T.B.).",
year = "2016",
month = aug,
day = "26",
doi = "10.1126/science.aaf1220",
language = "English",
volume = "353",
pages = "933--936",
journal = "Science",
issn = "0036-8075",
number = "6302",
}