Norovirus (NoV) and rotavirus (RV) are re-emerging enteric viruses polluting the environment and causing foodborne gastroenteritis outbreaks. These viruses are shed at high concentrations and very resistant in the environment, thus contaminating surface waters. Oysters are a high-risk food since they can concentrate virus by filter-feeding and express glycan motifs similar to histo-blood group antigens (HBGA), which are attachment factors for NoVs and RVs in their human host. Since distinct viral strains attach to different glycan motifs, the HBGA polymorphism in the human population dictates sensitivity to infection. The presence of some of the HBGA motifs in the oyster tissues could likewise contribute to the selective accumulation of virus strains. Similar ligands are also found at the surface of some bacteria, including bacteria present in seawater. Our main hypothesis is that glycan recognition by both NoVs and RVAs is a key determinant of their environmental behavior, selecting viral strains and affecting their diffusion, infectivity, stability and persistence. Depending on a given strain’s HBGA specificity the outcome might vastly differ. Thus, attachment of the virus particle to bacteria may increase (or decrease) the virus persistence. It may also facilitate (or impair) bioaccumulation in oyster and it might either facilitate or impair infection of human cells. Project GOyAVE has 3 objectives: characterizing virus glycan ligands of oysters and of bacteria; deciphering the role of these environmental HBGA in NoV and RV infection of human intestinal cells; and assessing their role in the persistence of infectious virus in oysters or on bacterial cells. Using advanced methods such as nanoparticles enabling controlled multivalent presentation of the carbohydrate-binding domains of virus strains, state of the art MS and NMR methods dedicated to glycome analysis, in situ hybridization for localization of bioaccumulated viruses, human enteroids to detect infectious norovirus, gut-on-a chip microfluidics enabling improved realistic virus culture and NGS analysis of bioaccumulated virus, GOyAVE will provide a global approach encompassing the molecular analysis levels, the cellular and tissular levels, up to the environment levels. For the three tasks, all identified bottlenecks have a solution proposed based on the complementarity and experience of the three partners in their respective fields. The impact of GOyAVE will benefit to fundamental science by improving the knowledge of NoV and RV biology and to applied food science as it will provide a better understanding of persistence of infectious human enteric viruses in oysters. By combining different approaches, GOyAVE will allow the development of several tools meeting the social and economic demand for safer food.