Intestinal Organoids as Models to Study Viruses: Current Application and Future Perspective

Intestinal organoids have emerged as a transformative model system in virology, bridging the gap between conventional cell lines and animal models by recapitulating the complex cellular diversity, three-dimensional architecture, and key functions of the human intestinal epithelium. This review highlights how this technology has enabled groundbreaking studies of enteric viruses, including the successful cultivation of previously uncultivable human norovirus, and has provided critical insights into the infection mechanisms of rotavirus, enterovirus A71, and Severe Acute Respiratory Syndrome Coronavirus 2. We discuss how emerging technologies, such as co-culture systems for host-microbiome interactions, vascularization techniques, and CRISPR/Cas9 gene editing, are being integrated with organoids to create more physiologically relevant microphysiological systems. Despite challenges related to immune component integration and model standardization, intestinal organoids offer a promising platform for elucidating virus-host interactions, advancing antiviral drug screening, and promoting personalized infectious disease research.