title: Antibodies against Lewis antigens inhibit the binding of human norovirus GII.4 virus-like particles to saliva but not to intestinal Caco-2 cells.
abstract: BACKGROUND
  Human noroviruses (NoVs) are the main cause of gastroenteritis worldwide. The most commonly detected NoV strains belong to the genetically diverse GII.4 genotype, with new pandemic variants emerging periodically. Despite extensive efforts, NoV investigation has been hampered by the lack of an effective in vitro cell culture system. However, NoV-derived recombinant virus-like particles (VLPs) resembling empty capsids are good surrogates for analysing NoV antigenicity and virus-ligand interactions. NoV VLPs have been reported to bind to histo-blood group antigens (HBGAs). We have analysed the ability of NoV VLPs derived from GI.1 genotype and from three GII.4 genotype variants, GII.4-1999, GII.4-2004 and GII.4-2006b, to bind to porcine gastric mucin (PGM), human saliva and differentiated human intestinal Caco-2 cells (D-Caco-2 cells).
  
  
  RESULTS
  Distinct patterns of saliva binding with the NoV GII.4 variant VLPs were observed, although they bound to D-Caco-2 cells independently of the expression of HBGAs. Monoclonal antibodies against Lewis antigens were able to block the binding of NoV VLPs to saliva, but not to D-Caco-2 cells. Blocking HBGAs on the surface of D-Caco-2 cells with specific monoclonal antibodies did not affect NoV VLP binding to cellular membranes. Co-localisation of Lewis y (Le(y)) and H-type 2 antigens with NoV VLPs was not observed by immunofluorescence assays.
  
  
  CONCLUSIONS
  Although the binding of NoV VLPs of GII.4 genotype variants to human saliva samples occur with distinct HBGA binding patterns and can be blocked by antibodies against Lewis antigens, their attachment to D-Caco-2 cells can be mediated by other receptors, which still need further investigation.
authors.affiliation: Department of Microbiology, School of Medicine, University of Valencia, Avda. Blasco Ibáñez, 17, 46010, Valencia, Spain.
authors.forename: Noelia
authors.initials: N
authors.lastname: Carmona-Vicente
authors.affiliation: Virus Reference Department, Public Health England, London, UK.|NIHR Health Protection Research Unit in Gastrointestinal Infections, University of Liverpool, Liverpool, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Allen
authors.affiliation: Department of Microbiology, School of Medicine, University of Valencia, Avda. Blasco Ibáñez, 17, 46010, Valencia, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Rodríguez-Díaz
authors.affiliation: CIMI, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.|NIHR Health Protection Research Unit in Gastrointestinal Infections, University of Liverpool, Liverpool, UK.
authors.forename: Miren
authors.initials: M
authors.lastname: Iturriza-Gómara
authors.affiliation: Department of Microbiology, School of Medicine, University of Valencia, Avda. Blasco Ibáñez, 17, 46010, Valencia, Spain. Javier.Buesa@uv.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Buesa
mesh_terms: D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000378:metabolism*; D018938:Caco-2 Cells; D002648:Child; D004847:Epithelial Cells / Q000821:virology*; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D007983:Lewis Blood Group Antigens; D008297:Male; D008875:Middle Aged; D029322:Norovirus / Q000502:physiology*; D011991:Receptors, Virus / Q000378:metabolism*; D012463:Saliva / Q000821:virology*; D013552:Swine; D053585:Virus Attachment
chemical_list: D001323:Autoantibodies; D007983:Lewis Blood Group Antigens; D011991:Receptors, Virus
keywords: Caco-2 cells; GII.4 genotype; Histo-blood group antigens (HBGAs); Human norovirus (NoV); Receptor binding; Virus-like particles (VLPs)