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, Herbert W. Virgin

Research output: Contribution to journalArticle

107 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 (US)
Pages (from-to)933-936
Number of pages4
JournalScience
Volume353
Issue number6302
DOIs
StatePublished - Aug 26 2016
Externally publishedYes

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    Orchard, R. C., Wilen, C. B., Doench, J. G., Baldridge, M. T., McCune, B. T., Lee, Y. C. J., Lee, S., Pruett-Miller, S. M., Nelson, C. A., Fremont, D. H., & Virgin, H. W. (2016). Discovery of a proteinaceous cellular receptor for a norovirus. Science, 353(6302), 933-936. https://doi.org/10.1126/science.aaf1220