Nature Communications (Dec 2022)
SARS-CoV-2 Spike triggers barrier dysfunction and vascular leak via integrins and TGF-β signaling
- Scott B. Biering,
- Francielle Tramontini Gomes de Sousa,
- Laurentia V. Tjang,
- Felix Pahmeier,
- Chi Zhu,
- Richard Ruan,
- Sophie F. Blanc,
- Trishna S. Patel,
- Caroline M. Worthington,
- Dustin R. Glasner,
- Bryan Castillo-Rojas,
- Venice Servellita,
- Nicholas T. N. Lo,
- Marcus P. Wong,
- Colin M. Warnes,
- Daniel R. Sandoval,
- Thomas Mandel Clausen,
- Yale A. Santos,
- Douglas M. Fox,
- Victoria Ortega,
- Anders M. Näär,
- Ralph S. Baric,
- Sarah A. Stanley,
- Hector C. Aguilar,
- Jeffrey D. Esko,
- Charles Y. Chiu,
- John E. Pak,
- P. Robert Beatty,
- Eva Harris
Affiliations
- Scott B. Biering
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley
- Francielle Tramontini Gomes de Sousa
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley
- Laurentia V. Tjang
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley
- Felix Pahmeier
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley
- Chi Zhu
- Department of Nutritional Sciences and Toxicology, University of California, Berkeley
- Richard Ruan
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley
- Sophie F. Blanc
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley
- Trishna S. Patel
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley
- Caroline M. Worthington
- Chan Zuckerberg Biohub
- Dustin R. Glasner
- Department of Laboratory Medicine, University of California, San Francisco
- Bryan Castillo-Rojas
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley
- Venice Servellita
- Department of Laboratory Medicine, University of California, San Francisco
- Nicholas T. N. Lo
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley
- Marcus P. Wong
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley
- Colin M. Warnes
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley
- Daniel R. Sandoval
- Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego
- Thomas Mandel Clausen
- Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego
- Yale A. Santos
- Department of Laboratory Medicine, University of California, San Francisco
- Douglas M. Fox
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley
- Victoria Ortega
- Department of Microbiology and Immunology, Cornell University
- Anders M. Näär
- Department of Nutritional Sciences and Toxicology, University of California, Berkeley
- Ralph S. Baric
- Department of Epidemiology, University of North Carolina at Chapel Hill
- Sarah A. Stanley
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley
- Hector C. Aguilar
- Department of Microbiology and Immunology, Cornell University
- Jeffrey D. Esko
- Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego
- Charles Y. Chiu
- Innovative Genomics Institute, University of California, Berkeley
- John E. Pak
- Chan Zuckerberg Biohub
- P. Robert Beatty
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley
- Eva Harris
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley
- DOI
- https://doi.org/10.1038/s41467-022-34910-5
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 19
Abstract
Severe COVID-19 is associated with epithelial and endothelial barrier dysfunction, however, the molecular pathways resulting in endothelial barrier dysfunction and vascular leakage are only sparsely understood. Here, Biering et al. show that SARS-CoV-2 spike protein is sufficient to induce barrier dysfunction and vascular leak. They show a role for integrins, TGF-beta, ECM remodeling enzymes, and glycosaminoglycans in this S-mediated barrier dysfunction.
