Discovery of a proteinaceous cellular receptor for a norovirus

Robert C. Orchard, Craig B. Wilen, John G. Doench, Megan T. Baldridge, Broc T. McCune, Ying Chiang J. Lee, Sanghyun Lee, Shondra M. Pruett-Miller, Christopher A. Nelson, Daved H. Fremont, Skip Virgin

Research output: Contribution to journalArticlepeer-review

164 Scopus citations

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.

Original languageEnglish
Pages (from-to)933-936
Number of pages4
JournalScience
Volume353
Issue number6302
DOIs
StatePublished - Aug 26 2016

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