Functional receptor molecules CD300lf and CD300ld within the CD300 family enable murine noroviruses to infect cells.
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.
Department of Virology II, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Kei
K
Haga
Department of Virology II, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Akira
A
Fujimoto
Department of Virology II, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Reiko
R
Takai-Todaka
Department of Virology II, National Institute of Infectious Diseases, Tokyo 208-0011, Japan; New Business Planning Division, Innovative Diagnostics Research Center, Denka Innovation Center, Denka Company Limited, Tokyo 194-8560, Japan.
Motohiro
M
Miki
Department of Virology II, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Yen Hai
YH
Doan
Department of Virology II, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Kosuke
K
Murakami
Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Masaru
M
Yokoyama
National Institute for Physiological Sciences, Aichi 444-8585, Japan.
Kazuyoshi
K
Murata
Section of Gene Therapy, Department of Aging Intervention, National Center for Geriatrics and Gerontology, Aichi 474-8511, Japan nakanish@ncgg.go.jp katayama@nih.go.jp.
Akira
A
Nakanishi
Department of Virology II, National Institute of Infectious Diseases, Tokyo 208-0011, Japan; nakanish@ncgg.go.jp katayama@nih.go.jp.
Kazuhiko
K
Katayama
D000595:Amino Acid Sequence; D000818:Animals; D017250:Caliciviridae Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D036022:Capsid Proteins / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D004198:Disease Susceptibility; D015870:Gene Expression; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D051379:Mice; D008958:Models, Molecular; D009154:Mutation; D029322:Norovirus / Q000502:physiology*; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D056189:Viral Tropism; D053585:Virus Attachment
C482560:CLM-1 protein, mouse; D036022:Capsid Proteins; D011971:Receptors, Immunologic; D011991:Receptors, Virus
CD300 molecules; CD300ld; CD300lf; murine norovirus; norovirus proteinaceous receptors
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