Activation of alveolar epithelial ER stress by β-coronavirus infection disrupts surfactant homeostasis in mice: implications for COVID-19 respiratory failure

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 327; no. 2; pp. L232 - L249
• Main Authors: Murthy, Aditi, Rodriguez, Luis R, Dimopoulos, Thalia, Bui, Sarah, Iyer, Swati, Chavez, Katrina, Tomer, Yaniv, Abraham, Valsamma, Cooper, Charlotte, Renner, David M, Katzen, Jeremy B, Bentley, Ian D, Ghadiali, Samir N, Englert, Joshua A, Weiss, Susan R, Beers, Michael F
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.08.2024
• Subjects: Alveolar Epithelial Cells - metabolism; Alveolar Epithelial Cells - pathology; Alveolar Epithelial Cells - virology; Alveoli; Animal models; Animals; Betacoronavirus; Bronchus; Cell activation; Cell culture; Cellular stress response; Coronavirus Infections - complications; Coronavirus Infections - metabolism; Coronavirus Infections - pathology; Coronavirus Infections - virology; Coronaviruses; COVID-19; COVID-19 - complications; COVID-19 - metabolism; COVID-19 - pathology; COVID-19 - virology; Disease Models, Animal; eIF-2 Kinase - metabolism; Endoplasmic reticulum; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Endoribonucleases - metabolism; Epithelial cells; Epithelium; Failure; Gas exchange; Hepatitis; Homeostasis; Humans; In vivo methods and tests; Infections; Injuries; Inositol; Inositols; Kinases; Lavage; Lungs; Mice; Murine hepatitis virus - pathogenicity; Protein folding; Protein Serine-Threonine Kinases - metabolism; Proteins; Pulmonary Surfactants - metabolism; Respiration; Respiratory diseases; Respiratory failure; Respiratory Insufficiency - metabolism; Respiratory Insufficiency - pathology; Respiratory Insufficiency - virology; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Surface tension; Surfactants; Unfolded Protein Response; Viral diseases; Weight loss; alveolar type 2 cell; SARS-CoV-2; mouse hepatitis virus-1 (MHV-1); transitional epithelial cell state; pulmonary surfactant

COVID-19 syndrome is characterized by acute lung injury, hypoxemic respiratory failure, and high mortality. Alveolar type 2 (AT2) cells are essential for gas exchange, repair, and regeneration of distal lung epithelium. We have shown that the causative agent, severe acute respiratory syndrome corona...