Infection of Distal Human Lung Epithelium with Sars-Cov-2
Coronavirus disease 2019 (COVID-19) is the most recent respiratory pandemic caused by coronavirus 2 associated with severe acute respiratory syndrome (SARS-CoV-2). Although the infection begins in the proximal airways, infection of the distal lung's alveolar type 2 (AT2) cells and associated inflammation causes severe and sometimes fatal symptoms. In this study, we create primary human lung epithelial infection models to better understand the proximal and distal lung epithelium's responses to SARS-CoV-2 infection. SARS-CoV-2 infects alveosphere cultures of distal lung AT2 cells, resulting in an epithelial cell-autonomous proinflammatory response with increased expression of interferon signaling genes. Remdesivir strongly suppresses viral infection/replication, according to studies to validate the efficacy of selected candidate COVID-19 drugs. We provide a relevant platform for the investigation of COVID-19 pathobiology as well as rapid drug screening against SARS-CoV-2 and emerging respiratory pathogens.