Generation of an Induced Pluripotent Stem Cell-Derived Alveolar Type II In Vitro Model to Study Influenza A Virus Infection and Drug Treatments.

Influenza viruses (IVs) represent a significant global health issue, capable of causing seasonal epidemics and occasional pandemics with substantial morbidity and mortality. The emergence of viral resistance further complicates treatment strategies. In this study, induced pluripotent stem cell-derived human alveolar type II (iAT2) cells are used to model influenza A virus (IAV) infection and to assess antiviral responses. Cultured at an air-liquid interface (ALI) in transwell systems, iAT2 cells recapitulate key features of the alveolar epithelium and support productive IAV replication. Upon infection, iAT2 cells mounted an antiviral transcriptional response and exhibited sensitivity to oseltamivir treatment, consistent with its established in vivo efficacy. Together, these findings highlight the utility of iAT2 cells as a scalable, physiologically relevant in vitro model for influenza research and antiviral drug testing. Future applications may include the evaluation of emerging viral strains and the development of personalized antiviral therapies.