Leveraging organoid models to understand mechanisms of viral infections and immunity in bats.

Bats are important reservoir hosts for zoonotic viruses owing to their unusual ability to avoid development of clinical disease and pathological lesions upon viral infection. Research efforts to understand the unique responses of bats to viral infection have been limited by the vast number of bat species and the lack of accessible experimental model systems. Over the past 5 years, organoid models, which are long-term cultures of primary cells, have been developed from gastrointestinal, respiratory and kidney tissues of multiple fruit-eating and insectivorous bats. Compared with human organoids, bat organoids showed increased expression of type I and type III interferon genes, other antiviral genes and complement genes at baseline and in response to viral stimulation. Bat organoids generally showed strong upregulation of interferon genes and interferon-stimulated genes in response to viruses. Conversely, the ability of bat organoids to support viral replication was dependent on the virus, tissue type and bat species. Overall, the recent progress in the field demonstrates the potential of organoids to serve as relevant models for exploring species- and tissue-specific responses to viruses in bats.