Modeling respiratory viral infections and investigating immune responses: new advances in human organ chip models

Respiratory viral infections pose persistent global health threats, yet traditionalin vitroand animal models inadequately recapitulate human tissue microenvironments. Organ-on-a-chip technology integrates microfluidic engineering with cell biology to recreate three-dimensional architectures, mechanical forces, and multicellular interactions of the human respiratory system. This review systematically summarizes recent advances in organ-on-a-chip platforms for modeling respiratory viral infections and host immune responses. We highlight their unique capabilities in simulating alveolar-capillary barriers, lymphoid follicle formation, and multi-organ axes including lung-brain and gut-lung communication. Furthermore, we discuss applications in antiviral drug screening, vaccine evaluation, and personalized medicine, while addressing current challenges and future directions toward standardized, multi-organ integrated, and intelligently monitored systems.