Functional receptor molecules CD300lf and CD300ld within the CD300 family enable murine noroviruses to infect cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 113; no. 41; pp. E6248 - E6255
• Main Authors: Haga, Kei, Fujimoto, Akira, Takai-Todaka, Reiko, Miki, Motohiro, Doan, Yen Hai, Murakami, Kosuke, Yokoyama, Masaru, Murata, Kazuyoshi, Nakanishi, Akira, Katayama, Kazuhiko
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 11-10-2016
• Series: PNAS Plus
• Subjects: Amino Acid Sequence; Amino acids; Animals; Biological Sciences; Caliciviridae Infections - genetics; Caliciviridae Infections - metabolism; Caliciviridae Infections - virology; Capsid Proteins - chemistry; Capsid Proteins - metabolism; Cell culture; Cell Line; Cells, Cultured; Disease Susceptibility; Gene Expression; Genomes; Host-Pathogen Interactions - genetics; Humans; Macrophages - metabolism; Macrophages - virology; Mice; Models, Molecular; Molecules; Mutation; Norovirus - physiology; PNAS Plus; Protein Binding; Protein Conformation; Protein Interaction Domains and Motifs; Protein Multimerization; Receptors, Immunologic - chemistry; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Receptors, Virus - chemistry; Receptors, Virus - genetics; Receptors, Virus - metabolism; Ribonucleic acid; RNA; Viral Tropism; Virus Attachment; Viruses; murine norovirus; CD300ld; norovirus proteinaceous receptors; CD300lf; CD300 molecules
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1605575113

Norovirus is the leading cause of acute gastroenteritis worldwide. Since the discovery of human norovirus (HuNoV), an efficient and reproducible norovirus replication system has not been established in cultured cells. Although limited amounts of virus particles can be produced when the HuNoV genome is directly transfected into cells, the HuNoV cycle of infection has not been successfully reproduced in any currently available cell-culture system. Those results imply that the identification of a functional cell-surface receptor for norovirus might be the key to establishing a norovirus culture system. Using a genome-wide CRISPR/Cas9 guide RNA library, we identified murine CD300lf and CD300ld as functional receptors for murine norovirus (MNV). The treatment of susceptible cells with polyclonal antibody against CD300lf significantly reduced the production of viral progeny. Additionally, ectopic CD300lf expression in nonsusceptible cell lines derived from other animal species enabled MNV infection and progeny production, suggesting that CD300lf has potential for dictating MNV host tropism. Furthermore, CD300ld, which has an amino acid sequence in the N-terminal region of its extracellular domain that is highly homologous to that of CD300lf, also functions as a receptor for MNV. Our results indicate that direct interaction of MNV with two cell-surface molecules, CD300lf and CD300ld, dictates permissive noroviral infection.