Bile-salt-stimulated lipase and mucins from milk of 'secretor' mothers inhibit the binding of Norwalk virus capsids to their carbohydrate ligands.
Breast-feeding-associated protection against calicivirus diarrhoea is associated with the presence of high levels of 2-linked oligosaccharides in mother's milk, and human calicivirus strains including the NV (Norwalk virus) use gut 2-linked fucosylated glycans as receptors, suggesting the presence of decoy receptors in milk. Our aim was to analyse the ability of human milk to inhibit the attachment of rNV VLPs (recombinant NV-like particles) to their carbohydrate ligands and to characterize potential inhibitors found in milk. Milk from women with the secretor phenotype was strongly inhibitory, unlike milk from women that are non-secretors, which is devoid of 2-linked fucosylated structures. At least two fractions in human milk acted as inhibitors for the NV capsid attachment. The first fraction corresponded to BSSL (bile-salt-stimulated lipase) and the second to associated mucins MUC1 and MUC4. These proteins present tandem repeat O-glycosylated sequences that should act as decoy receptors for the NV, depending on the combined mother/child secretor status.
Ruvoën-Clouet
Nathalie
N
INSERM U601, Institute of Biology, 9 Quai Moncousu, 44093 Nantes Cedex 01, France.
Mas
Eric
E
Marionneau
Séverine
S
Guillon
Patrice
P
Lombardo
Dominique
D
Le Pendu
Jacques
J
D000941:Antigens / Q000378:metabolism*; D000951:Antigens, Neoplasm; D036022:Capsid Proteins / Q000378:metabolism*; D002241:Carbohydrates; D004386:Duodenum / Q000166:cytology / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008049:Lipase / Q000378:metabolism*; D008895:Milk, Human / Q000737:chemistry* / Q000201:enzymology / Q000821:virology; D018396:Mucin-1; D055264:Mucin-4; D009077:Mucins / Q000378:metabolism*; D009663:Norwalk virus / Q000378:metabolism*; D011485:Protein Binding
D000941:Antigens; D000951:Antigens, Neoplasm; D036022:Capsid Proteins; D002241:Carbohydrates; D006023:Glycoproteins; D008024:Ligands; C060192:MUC1 protein, human; C524658:MUC4 protein, human; D018396:Mucin-1; D055264:Mucin-4; D009077:Mucins; C054621:CEL protein, human; D008049:Lipase