SARS-CoV-2 and COVID-19 Research
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Peer reviewed
Abstract
Abstract
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.
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@article{Liang2024Initiator,
title = {Initiator cell death event induced by SARS-CoV-2 in the human airway epithelium},
author = {Kaixin Liang and Katherine C. Barnett and Martin Hsu and Wei-Chun Chou and Sachendra S. Bais and Kristina J. Riebe and Yuying Xie and Tuong T. Nguyen and Thomas H. Oguin and Kevin M. Vannella and Stephen M. Hewitt and Daniel S. Chertow and Maria Blasi and Gregory D. Sempowski and Amelia Karlsson and Beverly H. Koller and Deborah J. Lenschow and Scott H. Randell and Jenny P.‐Y. Ting},
journal = {Science Immunology},
year = {2024},
doi = {10.1126/sciimmunol.adn0178},
url = {https://doi.org/10.1126/sciimmunol.adn0178}
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