Modeling reptile virus infection in vitro using Python regius airway organoids II

Through de novo assembly of a Python regius reference genome, we characterized airway organoids at single-cell resolution, revealing diverse cell populations including ionocytes, ciliated, goblet, club, endocrine, tuft, and basal cells. The organoids supported productive infection with ball python nidovirus (BPNV) and mounted a robust epithelial antiviral response through induction of interferon-stimulated genes, cytokines and genes involved in chemical defense.

As a proof-of-concept, antiviral drug treatment reduced BPNV levels, highlighting the model's utility for drug testing. By providing a reductionist system of the serpentine airway, these organoids constitute a physiologically relevant in vitro model to study reptile viruses and host–pathogen interactions in the native host. This system has potential veterinary applications, ecology of serpentes, and zoonotic disease research.