RTI uses cookies to offer you the best experience online. By clicking “accept” on this website, you opt in and you agree to the use of cookies. If you would like to know more about how RTI uses cookies and how to manage them please view our Privacy Policy here. You can “opt out” or change your mind by visiting: http://optout.aboutads.info/. Click “accept” to agree.
Initiator cell death event induced by SARS-CoV-2 in the human airway epithelium
Liang, K., Barnett, K. C., Hsu, M., Chou, W.-C., Bais, S. S., Riebe, K., Xie, Y., Nguyen, T. T., Oguin, T. H., Vannella, K. M., Hewitt, S. M., Chertow, D. S., Blasi, M., Sempowski, G. D., Karlsson, A., Koller, B. H., Lenschow, D. J., Randell, S. H., & Ting, J. P.-Y. (2024). Initiator cell death event induced by SARS-CoV-2 in the human airway epithelium. Science immunology, 9(97), eadn0178. Article eadn0178. https://doi.org/10.1126/sciimmunol.adn0178
Virus-induced cell death is a key contributor to COVID-19 pathology. Cell death induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is well studied in myeloid cells but less in its primary host cell type, angiotensin-converting enzyme 2 (ACE2)-expressing human airway epithelia (HAE). SARS-CoV-2 induces apoptosis, necroptosis, and pyroptosis in HAE organotypic cultures. Single-cell and limiting-dilution analysis revealed that necroptosis is the primary cell death event in infected cells, whereas uninfected bystanders undergo apoptosis, and pyroptosis occurs later during infection. Mechanistically, necroptosis is induced by viral Z-RNA binding to Z-DNA-binding protein 1 (ZBP1) in HAE and lung tissues from patients with COVID-19. The Delta (B.1.617.2) variant, which causes more severe disease than Omicron (B1.1.529) in humans, is associated with orders of magnitude-greater Z-RNA/ZBP1 interactions, necroptosis, and disease severity in animal models. Thus, Delta induces robust ZBP1-mediated necroptosis and more disease severity.
