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

## TL;DR

Researchers created a lab model using stem cells to study how influenza viruses infect lung cells and respond to drugs like oseltamivir.

## Contribution

This is the first study to demonstrate influenza A virus infection and drug response in induced pluripotent stem cell-derived alveolar type II cells.

## Key findings

- iAT2 cells grown at air–liquid interface support productive influenza A virus replication.
- iAT2 cells show antiviral transcriptional responses and respond to oseltamivir treatment.
- The model is scalable and physiologically relevant for influenza research and drug testing.

## Abstract

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.

Patient‐specific induced pluripotent stem cells (iPSCs) can be differentiated into alveolar type II cells (iAT2s), expanded as 3D alveolospheres, and grown at physiologically relevant air–liquid interface (ALI). This study shows for the first time the infectability of iAT2s by the influenza A virus (IAV) and proves their responsiveness to the well‐established anti‐influenza drug oseltamivir.