Using a novel cross-species organoid model to study PIV5 infection in vitro: a virus associated with disease in zoo animals

Although parainfluenza virus 5 (PIV5) has long been considered non-pathogenic in humans, it is increasingly linked to disease in zoo animals. However, its prevalence and pathogenesis in zoo animals remain poorly understood. Here, we developed the first respiratory organoid biobank from four key species-tiger, lesser panda, pony, and argali to dissect the underlying mechanisms. Comparative studies indicated that the lower respiratory organoids derived from zoo animals can supported PIV5 replication that mirrors the viral kinetics observed in natural infections, suggesting a degree of physiological relevance for studying host-pathogen interactions. We also demonstrated that PIV5 induces robust innate immune responses, activates caspase-3 to trigger cell apoptosis, and causes cell lysis in tiger lung organoid, whereas these effects were not observed in human lung organoid. Consistent with our in vitro findings, histopathological analysis of lung tissues from infected tiger confirmed the presence of caspase-3 activation, inflammatory cell infiltration, and necrotic cellular debris. Together, we established a zoo animal respiratory organoid platform to study host-pathogen interactions in tissues from the upper and lower respiratory tract.