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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
JournalScience
Volume353
Issue6302
Pages933-6
Date Published2016 08 26
ISSN1095-9203
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.

DOI10.1126/science.aaf1220
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/27540007?dopt=Abstract

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