Organoids in respiratory virus research: advances and perspectives

The pandemics of respiratory viruses pose a worldwide public health problem and bio-safety threat. Therefore, the development of high-throughput and accurate infection models is crucial for elucidating viral pathogenesis and accelerating countermeasures to address the evolving respiratory viruses and the unexpected outbreaks of emerging variants. Compared to traditional 2D cultures, organoids exhibit pronounced intercellular interactions, extracellular matrix signaling, and tissue-specific multicellular cooperation, thereby more accurately recapitulating the in vivo microphysiological environment. However, research involving animal models typically requires prolonged experimental timelines, making it challenging to perform high-throughput screening or rapidly develop therapeutic strategies within the valuable timeframe. Since the outbreak of SARS-CoV-2, organoids have significantly advanced basic virology research and demonstrated potential in replicating the pathological and immunological characteristics in human patients. This review provides a comprehensive summary of the theoretical foundations, methodological framework, and complete procedures for identification and validation in organoid construction, along with their applications in the investigation of various respiratory viruses, such as coronaviruses, the influenza virus, respiratory syncytial virus, and others. Overall, the development of organoids, in conjunction with the integration of interdisciplinary technologies, has significantly advanced our fundamental understanding of the immunopathology process of respiratory viral infections, improved research efficiency, and provided precise tools for translational medical research.