SARS-CoV-2 causes severe epithelial inflammation and barrier dysfunction
| Autor: | Andreas Henke, Jürgen Rödel, Sarah Böttcher, Franziska Hornung, Michael Schacke, Mike Marquet, Bettina Löffler, Paul M. Jordan, Regine Heller, Johannes Jungwirth, Sandor Nietzsche, Alexander S. Mosig, Mathias W. Pletz, Liane Giebeler, Oliver Werz, Roland Zell, Christian Brandt, Clio Häring, Christina Ehrhardt, Stefanie Deinhardt-Emmer |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Endothelium
viruses Immunology Viremia Inflammation Biology medicine.disease_cause Microbiology chip model 03 medical and health sciences 0302 clinical medicine Interferon epithelial/endothelial barrier Virology medicine 030212 general & internal medicine Barrier function 030304 developmental biology Coronavirus 0303 health sciences SARS-CoV-2 COVID-19 medicine.disease Virus-Cell Interactions interferons medicine.anatomical_structure Viral replication Insect Science medicine.symptom Viral load medicine.drug |
| Zdroj: | Journal of Virology |
| ISSN: | 1098-5514 |
| Popis: | SARS-CoV-2 challenges health care systems and societies worldwide in unprecedented ways. Although numerous new studies have been conducted, research to better understand the molecular pathogen-host interactions are urgently needed. Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be asymptomatic, but they can also be accompanied by a variety of symptoms that result in mild to severe coronavirus disease-19 (COVID-19) and are sometimes associated with systemic symptoms. Although the viral infection originates in the respiratory system, it is unclear how the virus can overcome the alveolar barrier, which is observed in severe COVID-19 disease courses. To elucidate the viral effects on the barrier integrity and immune reactions, we used mono-cell culture systems and a complex human chip model composed of epithelial, endothelial, and mononuclear cells. Our data show that SARS-CoV-2 efficiently infected epithelial cells with high viral loads and inflammatory response, including interferon expression. In contrast, the adjacent endothelial layer was neither infected nor did it show productive virus replication or interferon release. With prolonged infection, both cell types were damaged, and the barrier function deteriorated, allowing the viral particles to overbear. In our study, we demonstrate that although SARS-CoV-2 is dependent on the epithelium for efficient replication, the neighboring endothelial cells are affected, e.g., by the epithelial cytokines or components induced during infection, which further results in damage of the epithelial/endothelial barrier function and viral dissemination. IMPORTANCE SARS-CoV-2 challenges health care systems and societies worldwide in unprecedented ways. Although numerous new studies have been conducted, research to better understand the molecular pathogen-host interactions is urgently needed. For this, experimental models have to be developed and adapted. In the present study we used mono-cell culture systems, and we established a complex chip model, where epithelial and endothelial cells are cultured in close proximity. We demonstrate that epithelial cells can be infected with SARS-CoV-2, while the endothelium did not show any infection signs. Since SARS-CoV-2 is able to establish viremia, the link to thromboembolic events in severe COVID-19 courses is evident. However, whether the endothelial layer is damaged by the viral pathogens or whether other endothelial-independent homeostatic factors are induced by the virus is essential for understanding the disease development. Therefore, our study is important, as it demonstrates that the endothelial layer could not be infected by SARS-CoV-2 in our in vitro experiments, but we were able to show the destruction of the epithelial-endothelial barrier in our chip model. From our experiments, we can assume that virus-induced host factors disturbed the epithelial-endothelial barrier function and thereby promote viral spread. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|