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.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Orchard
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Craig B
authors.initials: CB
authors.lastname: Wilen
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: Doench
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Megan T
authors.initials: MT
authors.lastname: Baldridge
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Broc T
authors.initials: BT
authors.lastname: McCune
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Ying-Chiang J
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Sanghyun
authors.initials: S
authors.lastname: Lee
authors.affiliation: Genome Engineering and iPSC Center, Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Shondra M
authors.initials: SM
authors.lastname: Pruett-Miller
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Nelson
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Daved H
authors.initials: DH
authors.lastname: Fremont
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. virgin@wustl.edu.
authors.forename: Herbert W
authors.initials: HW
authors.lastname: Virgin
mesh_terms: D000818:Animals; D017250:Caliciviridae Infections / Q000821:virology*; D018360:Crystallography, X-Ray; D005759:Gastroenteritis / Q000821:virology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D029322:Norovirus / Q000502:physiology*; D000072417:Protein Domains; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: C482560:CLM-1 protein, mouse; D011971:Receptors, Immunologic