tetano
Editor, Senior Moderator
Sci Immunol
. 2024 Jul 12;9(97):eadn0178.
doi: 10.1126/sciimmunol.adn0178. Epub 2024 Jul 12. Initiator cell death event induced by SARS-CoV-2 in the human airway epithelium
Kaixin Liang[SUP] 1 2 3 4 5 [/SUP], Katherine C Barnett[SUP] 1 2 3 4 [/SUP], Martin Hsu[SUP] 1 2 3 4 [/SUP], Wei-Chun Chou[SUP] 1 2 3 4 [/SUP], Sachendra S Bais[SUP] 6 [/SUP], Kristina Riebe[SUP] 7 [/SUP], Yuying Xie[SUP] 8 9 [/SUP], Tuong Thien Nguyen[SUP] 10 [/SUP], Thomas H Oguin 3rd[SUP] 7 [/SUP], Kevin M Vannella[SUP] 11 12 [/SUP], Stephen M Hewitt[SUP] 13 [/SUP], Daniel S Chertow[SUP] 11 12 [/SUP], Maria Blasi[SUP] 7 14 [/SUP], Gregory D Sempowski[SUP] 7 [/SUP], Amelia Karlsson[SUP] 7 [/SUP], Beverly H Koller[SUP] 1 2 [/SUP], Deborah J Lenschow[SUP] 6 15 16 [/SUP], Scott H Randell[SUP] 10 [/SUP], Jenny P-Y Ting[SUP] 1 2 3 4 [/SUP]
Affiliations
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.
. 2024 Jul 12;9(97):eadn0178.
doi: 10.1126/sciimmunol.adn0178. Epub 2024 Jul 12. Initiator cell death event induced by SARS-CoV-2 in the human airway epithelium
Kaixin Liang[SUP] 1 2 3 4 5 [/SUP], Katherine C Barnett[SUP] 1 2 3 4 [/SUP], Martin Hsu[SUP] 1 2 3 4 [/SUP], Wei-Chun Chou[SUP] 1 2 3 4 [/SUP], Sachendra S Bais[SUP] 6 [/SUP], Kristina Riebe[SUP] 7 [/SUP], Yuying Xie[SUP] 8 9 [/SUP], Tuong Thien Nguyen[SUP] 10 [/SUP], Thomas H Oguin 3rd[SUP] 7 [/SUP], Kevin M Vannella[SUP] 11 12 [/SUP], Stephen M Hewitt[SUP] 13 [/SUP], Daniel S Chertow[SUP] 11 12 [/SUP], Maria Blasi[SUP] 7 14 [/SUP], Gregory D Sempowski[SUP] 7 [/SUP], Amelia Karlsson[SUP] 7 [/SUP], Beverly H Koller[SUP] 1 2 [/SUP], Deborah J Lenschow[SUP] 6 15 16 [/SUP], Scott H Randell[SUP] 10 [/SUP], Jenny P-Y Ting[SUP] 1 2 3 4 [/SUP]
Affiliations
- PMID: 38996010
- DOI: 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.