Norovirus inter-species transmission in an ex vivo model is dependent on virus internalization capacity

Human noroviruses (HuNoV) are the most common cause of viral gastroenteritis worldwide, causing sporadic cases and outbreaks. Noroviruses that infect wild and domestic animals, including pigs and dogs, are genetically related to human noroviruses, increasing the potential for cross-species transmission. To investigate the potential of noroviruses to cross the species barrier, we used porcine, canine, and avian precision-cut intestinal slices. We show that human norovirus virus-like particles (VLPs) bind to pig and dog intestinal tissue and are taken up with a similar efficiency as the porcine and canine noroviruses, respectively. In contrast, no binding or internalization of human, porcine, or canine noroviruses was detected in chicken tissue. We further showed that human norovirus replicates in pig intestinal tissue. In contrast, while animal noroviruses attached to human intestinal cells, intracellular uptake was limited. This suggests that human-to-animal transmission is more likely than animal-to-human transmission and that viral uptake likely presents a species barrier.