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- Lilian Schimmel
- Institute for Molecular Bioscience, Division of Cell and Developmental Biology The University of Queensland Brisbane QLD Australia
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- Keng Yih Chew
- School of Chemistry and Molecular Biosciences The University of Queensland Brisbane QLD Australia
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- Claudia J Stocks
- Institute for Molecular Bioscience, Division of Cell and Developmental Biology The University of Queensland Brisbane QLD Australia
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- Teodor E Yordanov
- Institute for Molecular Bioscience, Division of Cell and Developmental Biology The University of Queensland Brisbane QLD Australia
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- Patricia Essebier
- Institute for Molecular Bioscience, Division of Cell and Developmental Biology The University of Queensland Brisbane QLD Australia
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- Arutha Kulasinghe
- The University of Queensland Diamantina Institute The University of Queensland Brisbane QLD Australia
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- James Monkman
- School of Biomedical Science, Faculty of Health Queensland University of Technology Brisbane QLD Australia
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- Anna Flavia Ribeiro dos Santos Miggiolaro
- Postgraduate Program of Health Sciences School of Medicine Hospital Marcelino Champagnat ‐ Pontifícia Universidade Católica do Paraná (PUCPR) Curitiba Brazil
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- Caroline Cooper
- Pathology Queensland Princess Alexandra Hospital Brisbane QLD Australia
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- Lucia de Noronha
- School of Medicine & Center of Education, Research and Innovation Hospital Marcelino Champagnat ‐ Pontifícia Universidade Católica do Paraná (PUCPR) Curitiba Brazil
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- Kate Schroder
- Institute for Molecular Bioscience, Division of Cell and Developmental Biology The University of Queensland Brisbane QLD Australia
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- Anne Karine Lagendijk
- Institute for Molecular Bioscience, Division of Cell and Developmental Biology The University of Queensland Brisbane QLD Australia
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- Larisa I Labzin
- Institute for Molecular Bioscience, Division of Cell and Developmental Biology The University of Queensland Brisbane QLD Australia
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- Kirsty R Short
- School of Chemistry and Molecular Biosciences The University of Queensland Brisbane QLD Australia
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- Emma J Gordon
- Institute for Molecular Bioscience, Division of Cell and Developmental Biology The University of Queensland Brisbane QLD Australia
説明
<jats:title>Abstract</jats:title><jats:sec><jats:title>Objectives</jats:title><jats:p>Thrombotic and microvascular complications are frequently seen in deceased COVID‐19 patients. However, whether this is caused by direct viral infection of the endothelium or inflammation‐induced endothelial activation remains highly contentious.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Here, we use patient autopsy samples, primary human endothelial cells and an <jats:italic>in vitro</jats:italic> model of the pulmonary epithelial–endothelial cell barrier.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We show that primary human endothelial cells express very low levels of the SARS‐CoV‐2 receptor ACE2 and the protease TMPRSS2, which blocks their capacity for productive viral infection, and limits their capacity to produce infectious virus. Accordingly, endothelial cells can only be infected when they overexpress ACE2, or are exposed to very high concentrations of SARS‐CoV‐2. We also show that SARS‐CoV‐2 does not infect endothelial cells in 3D vessels under flow conditions. We further demonstrate that in a co‐culture model endothelial cells are not infected with SARS‐CoV‐2. Endothelial cells do however sense and respond to infection in the adjacent epithelial cells, increasing ICAM‐1 expression and releasing pro‐inflammatory cytokines.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Taken together, these data suggest that <jats:italic>in vivo,</jats:italic> endothelial cells are unlikely to be infected with SARS‐CoV‐2 and that infection may only occur if the adjacent pulmonary epithelium is denuded (basolateral infection) or a high viral load is present in the blood (apical infection). In such a scenario, whilst SARS‐CoV‐2 infection of the endothelium can occur, it does not contribute to viral amplification. However, endothelial cells may still play a key role in SARS‐CoV‐2 pathogenesis by sensing adjacent infection and mounting a pro‐inflammatory response to SARS‐CoV‐2.</jats:p></jats:sec>
収録刊行物
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- Clinical & Translational Immunology
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Clinical & Translational Immunology 10 (10), e1350-, 2021-01
Wiley