Human noroviruses attach to intestinal tissue of a broad range of animal species.

Human noroviruses are the most common non-bacterial cause of gastroenteritis outbreaks with new variants and genotypes frequently emerging. The origin of these new viruses is unknown; however, animals have been proposed as a potential source as human noroviruses have been detected in animal species. Here we investigated the potential of animals to serve as reservoir of human noroviruses, by testing noroviruses attachment to formalin-fixed intestinal tissues of a range of potential reservoir animals. We set up a novel method to study norovirus binding using fluorescein isothiocyanate (FITC)-labelled virus-like particles. In humans, noroviruses interact with histo-blood group antigens (HBGAs), carbohydrates that are expressed, among others, on the epithelial lining of the gastrointestinal tract. In animals, this interaction is not well understood. To test if virus binding depends on HBGAs, we characterized the HBGA phenotype in animal tissues by immunohistochemistry. With the exception of the black-headed gull and the straw-coloured fruitbat, we observed attachment of several human norovirus genotypes to the intestinal epithelium of all tested animal species. We did, however, not find an association between the expression of a specific HBGA phenotype and VLP attachment. We show that selected human noroviruses can attach to small intestinal tissues across species, supporting the hypothesis that human noroviruses could reside in an animal reservoir. However, whether this attachment can subsequently lead to infection, needs to be further assessed.IMPORTANCE Noroviruses are a major cause of acute gastroenteritis in humans. New norovirus variants and recombinants (re-)emerge regularly in the human population. From animal experiments and surveillance studies it has become clear that at least seven animal models are susceptible to infection with human strains and that domesticated and wild animals shed human noroviruses in their faeces. As virus attachment is a first important step for infection we used a novel method utilising FITC-labelled VLPs to test for norovirus attachment to intestinal tissues of potential animal hosts. We further characterized these tissues with regards to their HBGA expression, a well-studied norovirus susceptibility factor in humans. We found attachment of several human strains to a variety of animal species independent of their HBGA phenotype. This supports the hypothesis that human strains could reside in an animal reservoir.