title: Epitopes in the P2 domain of norovirus VP1 recognized by monoclonal antibodies that block cell interactions.
abstract: Noroviruses cause the majority of epidemic outbreaks of acute viral gastroenteritis worldwide. Human norovirus strains do not grow in cell culture, but recent carbohydrate binding, sequence and structural analyses have begun to define functional domains in the norovirus capsid that may be conserved among multiple antigenic types. The purpose of this study was to localize domains and define sequences in the major capsid protein VP1 that are important for cell interactions. Monoclonal antibodies to genogroups GI.1 and GII.2 reference strains Norwalk virus and Snow Mountain virus, respectively, were generated that blocked binding of recombinant virus-like particles to Caco-2 intestinal cells and inhibited haemagglutination. Peptides that mimicked the mAb binding epitopes were selected from a phage-displayed random nonapeptide library. Anti-recombinant Norwalk virus mAb 54.6 and anti-recombinant Snow Mountain virus mAb 61.21 recognized epitopes located in the protruding P2 domain of VP1. The epitope recognized by mAb 61.21 contained amino acids that are completely conserved among norovirus strains across genogroups, including strains isolated from swine, bovine and murine species. This study identifies the first epitope involved in inhibition of norovirus-cell interactions and supports increasing evidence that interactions between noroviruses and host cells rely on structures in the P2 domain of VP1.
authors.affiliation: Veterinary Molecular Biology Laboratory, Montana State University, PO Box 173610, Bozeman, MT 59717, USA.
authors.forename: Vance P
authors.initials: VP
authors.lastname: Lochridge
authors.affiliation: Veterinary Molecular Biology Laboratory, Montana State University, PO Box 173610, Bozeman, MT 59717, USA.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Jutila
authors.affiliation: Veterinary Molecular Biology Laboratory, Montana State University, PO Box 173610, Bozeman, MT 59717, USA.
authors.forename: Joel W
authors.initials: JW
authors.lastname: Graff
authors.affiliation: Veterinary Molecular Biology Laboratory, Montana State University, PO Box 173610, Bozeman, MT 59717, USA.
authors.forename: Michele E
authors.initials: ME
authors.lastname: Hardy
mesh_terms: D000371:Agglutination; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral; D000918:Antibody Specificity; D018938:Caco-2 Cells; D036022:Capsid Proteins / Q000276:immunology / Q000378:metabolism*; D002450:Cell Communication / Q000276:immunology / Q000502:physiology*; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D029322:Norovirus / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D036022:Capsid Proteins; D000939:Epitopes; D011994:Recombinant Proteins