Early cell autonomous and niche-mediated alveolar epithelial response to influenza infection in primary lung organoids

Alveolar type 2 (AT2) cells are the preferential target of IAV as part of the pathogenesis of viral pneumonia and acute respiratory distress syndrome (ARDS). Early IAV infection of alveolar cells has been challenging to model both in vitro and in vivo.

To address this challenge, we used a combination of murine and human primary alveolar organoids to define methods for robust IAV infection and evaluated cell-autonomous consequences of IAV using a temporal series of multiome paired single nuclei RNA/ATAC sequencing. Infected AT2 cells undergo conserved changes defined by early loss of surfactant secretion, decreased lipid biogenesis, a rapid burst of antiviral response, and late viral-mediated suppression.