Norovirus recognizes histo-blood group antigens on gastrointestinal cells of clams, mussels, and oysters: A possible mechanism of bioaccumulation

Outbreaks of norovirus (NoV) gastroenteritis are often associated with the consumption of' contaminated bivalves such as oysters, clams, and mussels. Crassostrea virginica oysters trap the Norwalk virus through the intestinal type A-like histo-blood group antigen (HBGA), a possible mechanism of bioaccumulation responsible for NoV outbreaks. In this study, we tested binding and inhibition of binding in three species of oysters and one species each of clams and mussels with. NoVs, representing four HBGA receptor-binding patterns. Our results indicated that all three oyster species expressed type A- and type O-like HBGA in their gastrointestinal tissue. Similar type A-like antigens also were found in mussels and clams, but only some of them express the O-like antigens. Both genogroups I and II recombinant norovirus-like particles (rNoVLPs) bound to gastrointestinal homogenates from oysters, mussels, and clams, and the binding was inhibited by preincubation of the rNoVLP with HBGA-specific monoclonal antibodies or with types A or O HBGA-positive human saliva. Co-localization of rNoVLPs and HBGA on gastrointestinal epithelial cells of oysters, mussels, and clams was also observed by immunofluorescent microscopy. Finally, the binding of rNoVLP to oyster gastrointestinal homogenates was inhibited by incubation with HBGA analogs. This study significantly expands our understanding that multiple HBGAs are expressed in oyster, mussel, and clam gastrointestinal tissues, which could be the major mechanism of bioaccumulation of NoVs by these bivalves. Our results also suggest that this bioaccumulation could be reversed by incubation with HBGA analogs, a possible important new strategy for depuration.