CD300lf is the primary physiologic receptor of murine norovirus but not human norovirus

Autoři: Vincent R. Graziano aff001;  Forrest C. Walker aff002;  Elizabeth A. Kennedy aff002;  Jin Wei aff001;  Khalil Ettayebi aff003;  Madison S. Strine aff001;  Renata B. Filler aff001;  Ebrahim Hassan aff002;  Leon L. Hsieh aff004;  Arthur S. Kim aff002;  Abimbola O. Kolawole aff005;  Christiane E. Wobus aff005;  Lisa C. Lindesmith aff006;  Ralph S. Baric aff006;  Mary K. Estes aff003;  Robert C. Orchard aff007;  Megan T. Baldridge aff002;  Craig B. Wilen aff001
Působiště autorů: Departments of Laboratory Medicine and Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America aff001;  Department of Medicine, Division of Infectious Diseases, Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, Saint Louis, Missouri, United States of America aff002;  Departments of Medicine and Molecular Virology & Microbiology, Baylor College of Medicine, Houston, Texas, United States of America aff003;  Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America aff004;  Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America aff005;  Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, United States of America aff006;  Department of Immunology, University of Texas Southwestern Medical School, Dallas, Texas, United States of America aff007
Vyšlo v časopise: CD300lf is the primary physiologic receptor of murine norovirus but not human norovirus. PLoS Pathog 16(4): e1008242. doi:10.1371/journal.ppat.1008242
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008242


Murine norovirus (MNoV) is an important model of human norovirus (HNoV) and mucosal virus infection more broadly. Viral receptor utilization is a major determinant of cell tropism, host range, and pathogenesis. The bona fide receptor for HNoV is unknown. Recently, we identified CD300lf as a proteinaceous receptor for MNoV. Interestingly, its paralogue CD300ld was also sufficient for MNoV infection in vitro. Here we explored whether CD300lf is the sole physiologic receptor in vivo and whether HNoV can use a CD300 ortholog as an entry receptor. We report that both CD300ld and CD300lf are sufficient for infection by diverse MNoV strains in vitro. We further demonstrate that CD300lf is essential for both oral and parenteral MNoV infection and to elicit anti-MNoV humoral responses in vivo. In mice deficient in STAT1 signaling, CD300lf is required for MNoV-induced lethality. Finally, we demonstrate that human CD300lf (huCD300lf) is not essential for HNoV infection, nor does huCD300lf inhibit binding of HNoV virus-like particles to glycans. Thus, we report huCD300lf is not a receptor for HNoV.

Klíčová slova:

Colon – Ileum – Mammalian genomics – Norovirus – Receptor physiology – RNA extraction – Spleen – Viral genome


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