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Initiator cell death event induced by SARS-CoV-2 in the human airway epithelium.
Liang, Kaixin; Barnett, Katherine C; Hsu, Martin; Chou, Wei-Chun; Bais, Sachendra S; Riebe, Kristina; Xie, Yuying; Nguyen, Tuong Thien; Oguin, Thomas H; Vannella, Kevin M; Hewitt, Stephen M; Chertow, Daniel S; Blasi, Maria; Sempowski, Gregory D; Karlsson, Amelia; Koller, Beverly H; Lenschow, Deborah J; Randell, Scott H; Ting, Jenny P-Y.
Afiliación
  • Liang K; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Barnett KC; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Hsu M; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Chou WC; Center for Translational Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Bais SS; Oral and Craniofacial Biomedicine Program, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Riebe K; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Xie Y; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Nguyen TT; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Oguin TH; Center for Translational Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Vannella KM; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Hewitt SM; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Chertow DS; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Blasi M; Center for Translational Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Sempowski GD; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Karlsson A; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Koller BH; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Lenschow DJ; Center for Translational Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Randell SH; Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63130, USA.
  • Ting JP; Duke Human Vaccine Institute, Durham, NC 27701, USA.
Sci Immunol ; 9(97): eadn0178, 2024 Jul 12.
Article en En | MEDLINE | ID: mdl-38996010
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Unión al ARN / Mucosa Respiratoria / Piroptosis / Necroptosis / SARS-CoV-2 / COVID-19 Límite: Animals / Humans Idioma: En Revista: Sci Immunol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Unión al ARN / Mucosa Respiratoria / Piroptosis / Necroptosis / SARS-CoV-2 / COVID-19 Límite: Animals / Humans Idioma: En Revista: Sci Immunol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos