title: Human noroviruses recognize sialyl Lewis x neoglycoprotein.
abstract: The carbohydrate binding characteristics of a norovirus GII.3 (Chron1) and a GII.4 (Dijon) strain were investigated using virus-like particles (VLPs) and saliva samples from 81 individuals genotyped for FUT2 (secretor) and FUT3 (Lewis) and phenotyped for ABO and Lewis blood groups. The two VLPs showed a typical secretor-gene-dependent binding and bound significantly stronger to saliva from A, B, and AB than from O individuals (P < 0.0001 and P < 0.001) but did not bind to any samples from secretor-negative individuals. The GII.3 strain showed larger interindividual variation and bound stronger to saliva from B than from A(2) secretors (P < 0.01). When assaying for binding to neoglycoproteins, the GII.3 and GII.4 strains were compared with the Norwalk GI.1 prototype strain. Although all three strains bound to Lewis b (and H type 1 chain) glycoconjugates, only the two GII strains showed an additional binding to sialyl Lewis x. This novel binding was specific since the VLPs did not bind to structural analogs, e.g., Lewis x or sialyl Lewis a, but only to sialyl Lewis x, sialyl diLewis x and sialylated type 2 chain conjugates. In inhibition experiments, the sialyl Lewis x conjugate was the most potent inhibitor. The minimal requirement for this potential receptor structure is Neu5Ac alpha 3Gal beta 4(Fuc alpha 3)GlcNAc beta 3Gal beta- where Fuc is not absolutely necessary for binding. Our study shows that some human norovirus GII strains have at least two binding specificities: one secretor-gene-dependent related to alpha1,2-fucosylated carbohydrates and another related to alpha2,3-sialylated carbohydrates of the type 2 chain, e.g., sialyl Lewis x.
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: Gustaf E
authors.initials: GE
authors.lastname: Rydell
authors.forename: Jonas
authors.initials: J
authors.lastname: Nilsson
authors.forename: Jesus
authors.initials: J
authors.lastname: Rodriguez-Diaz
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ruvoën-Clouet
authors.forename: Lennart
authors.initials: L
authors.lastname: Svensson
authors.forename: Jacques
authors.initials: J
authors.lastname: Le Pendu
authors.forename: Göran
authors.initials: G
authors.lastname: Larson
mesh_terms: D001665:Binding Sites; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D029322:Norovirus / Q000235:genetics / Q000502:physiology*; D009844:Oligosaccharides / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D015203:Reproducibility of Results; D012463:Saliva / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen; D053585:Virus Attachment
chemical_list: D006023:Glycoproteins; D007983:Lewis Blood Group Antigens; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen