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Science DOI:10.1126/science.aaf1220

Discovery of a proteinaceous cellular receptor for a norovirus.

Publication TypeJournal Article
Year of Publication2016
AuthorsOrchard, RC, Wilen, CB, Doench, JG, Baldridge, MT, McCune, BT, Lee, Y-CJ, Lee, S, Pruett-Miller, SM, Nelson, CA, Fremont, DH, Virgin, HW
Date Published2016 08 26

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.


Alternate JournalScience
PubMed ID27540007
Grant ListU19 AI109725 / AI / NIAID NIH HHS / United States
P30 CA091842 / CA / NCI NIH HHS / United States
F31 CA177194 / CA / NCI NIH HHS / United States
T32 CA009547 / CA / NCI NIH HHS / United States