Cargando…
Increased susceptibility of human endothelial cells to infections by SARS-CoV-2 variants
Coronavirus disease 2019 (COVID-19) spawned a global health crisis in late 2019 and is caused by the novel coronavirus SARS-CoV-2. SARS-CoV-2 infection can lead to elevated markers of endothelial dysfunction associated with higher risk of mortality. It is unclear whether endothelial dysfunction is c...
Autores principales: | , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256413/ https://www.ncbi.nlm.nih.gov/pubmed/34224022 http://dx.doi.org/10.1007/s00395-021-00882-8 |
_version_ | 1783718098977685504 |
---|---|
author | Wagner, Julian U. G. Bojkova, Denisa Shumliakivska, Mariana Luxán, Guillermo Nicin, Luka Aslan, Galip S. Milting, Hendrik Kandler, Joshua D. Dendorfer, Andreas Heumueller, Andreas W. Fleming, Ingrid Bibli, Sofia-Iris Jakobi, Tobias Dieterich, Christoph Zeiher, Andreas M. Ciesek, Sandra Cinatl, Jindrich Dimmeler, Stefanie |
author_facet | Wagner, Julian U. G. Bojkova, Denisa Shumliakivska, Mariana Luxán, Guillermo Nicin, Luka Aslan, Galip S. Milting, Hendrik Kandler, Joshua D. Dendorfer, Andreas Heumueller, Andreas W. Fleming, Ingrid Bibli, Sofia-Iris Jakobi, Tobias Dieterich, Christoph Zeiher, Andreas M. Ciesek, Sandra Cinatl, Jindrich Dimmeler, Stefanie |
author_sort | Wagner, Julian U. G. |
collection | PubMed |
description | Coronavirus disease 2019 (COVID-19) spawned a global health crisis in late 2019 and is caused by the novel coronavirus SARS-CoV-2. SARS-CoV-2 infection can lead to elevated markers of endothelial dysfunction associated with higher risk of mortality. It is unclear whether endothelial dysfunction is caused by direct infection of endothelial cells or is mainly secondary to inflammation. Here, we investigate whether different types of endothelial cells are susceptible to SARS-CoV-2. Human endothelial cells from different vascular beds including umbilical vein endothelial cells, coronary artery endothelial cells (HCAEC), cardiac and lung microvascular endothelial cells, or pulmonary arterial cells were inoculated in vitro with SARS-CoV-2. Viral spike protein was only detected in HCAECs after SARS-CoV-2 infection but not in the other endothelial cells tested. Consistently, only HCAEC expressed the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2), required for virus infection. Infection with the SARS-CoV-2 variants B.1.1.7, B.1.351, and P.2 resulted in significantly higher levels of viral spike protein. Despite this, no intracellular double-stranded viral RNA was detected and the supernatant did not contain infectious virus. Analysis of the cellular distribution of the spike protein revealed that it co-localized with endosomal calnexin. SARS-CoV-2 infection did induce the ER stress gene EDEM1, which is responsible for clearance of misfolded proteins from the ER. Whereas the wild type of SARS-CoV-2 did not induce cytotoxic or pro-inflammatory effects, the variant B.1.1.7 reduced the HCAEC cell number. Of the different tested endothelial cells, HCAECs showed highest viral uptake but did not promote virus replication. Effects on cell number were only observed after infection with the variant B.1.1.7, suggesting that endothelial protection may be particularly important in patients infected with this variant. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00395-021-00882-8. |
format | Online Article Text |
id | pubmed-8256413 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-82564132021-07-06 Increased susceptibility of human endothelial cells to infections by SARS-CoV-2 variants Wagner, Julian U. G. Bojkova, Denisa Shumliakivska, Mariana Luxán, Guillermo Nicin, Luka Aslan, Galip S. Milting, Hendrik Kandler, Joshua D. Dendorfer, Andreas Heumueller, Andreas W. Fleming, Ingrid Bibli, Sofia-Iris Jakobi, Tobias Dieterich, Christoph Zeiher, Andreas M. Ciesek, Sandra Cinatl, Jindrich Dimmeler, Stefanie Basic Res Cardiol Original Contribution Coronavirus disease 2019 (COVID-19) spawned a global health crisis in late 2019 and is caused by the novel coronavirus SARS-CoV-2. SARS-CoV-2 infection can lead to elevated markers of endothelial dysfunction associated with higher risk of mortality. It is unclear whether endothelial dysfunction is caused by direct infection of endothelial cells or is mainly secondary to inflammation. Here, we investigate whether different types of endothelial cells are susceptible to SARS-CoV-2. Human endothelial cells from different vascular beds including umbilical vein endothelial cells, coronary artery endothelial cells (HCAEC), cardiac and lung microvascular endothelial cells, or pulmonary arterial cells were inoculated in vitro with SARS-CoV-2. Viral spike protein was only detected in HCAECs after SARS-CoV-2 infection but not in the other endothelial cells tested. Consistently, only HCAEC expressed the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2), required for virus infection. Infection with the SARS-CoV-2 variants B.1.1.7, B.1.351, and P.2 resulted in significantly higher levels of viral spike protein. Despite this, no intracellular double-stranded viral RNA was detected and the supernatant did not contain infectious virus. Analysis of the cellular distribution of the spike protein revealed that it co-localized with endosomal calnexin. SARS-CoV-2 infection did induce the ER stress gene EDEM1, which is responsible for clearance of misfolded proteins from the ER. Whereas the wild type of SARS-CoV-2 did not induce cytotoxic or pro-inflammatory effects, the variant B.1.1.7 reduced the HCAEC cell number. Of the different tested endothelial cells, HCAECs showed highest viral uptake but did not promote virus replication. Effects on cell number were only observed after infection with the variant B.1.1.7, suggesting that endothelial protection may be particularly important in patients infected with this variant. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00395-021-00882-8. Springer Berlin Heidelberg 2021-07-05 2021 /pmc/articles/PMC8256413/ /pubmed/34224022 http://dx.doi.org/10.1007/s00395-021-00882-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Contribution Wagner, Julian U. G. Bojkova, Denisa Shumliakivska, Mariana Luxán, Guillermo Nicin, Luka Aslan, Galip S. Milting, Hendrik Kandler, Joshua D. Dendorfer, Andreas Heumueller, Andreas W. Fleming, Ingrid Bibli, Sofia-Iris Jakobi, Tobias Dieterich, Christoph Zeiher, Andreas M. Ciesek, Sandra Cinatl, Jindrich Dimmeler, Stefanie Increased susceptibility of human endothelial cells to infections by SARS-CoV-2 variants |
title | Increased susceptibility of human endothelial cells to infections by SARS-CoV-2 variants |
title_full | Increased susceptibility of human endothelial cells to infections by SARS-CoV-2 variants |
title_fullStr | Increased susceptibility of human endothelial cells to infections by SARS-CoV-2 variants |
title_full_unstemmed | Increased susceptibility of human endothelial cells to infections by SARS-CoV-2 variants |
title_short | Increased susceptibility of human endothelial cells to infections by SARS-CoV-2 variants |
title_sort | increased susceptibility of human endothelial cells to infections by sars-cov-2 variants |
topic | Original Contribution |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256413/ https://www.ncbi.nlm.nih.gov/pubmed/34224022 http://dx.doi.org/10.1007/s00395-021-00882-8 |
work_keys_str_mv | AT wagnerjulianug increasedsusceptibilityofhumanendothelialcellstoinfectionsbysarscov2variants AT bojkovadenisa increasedsusceptibilityofhumanendothelialcellstoinfectionsbysarscov2variants AT shumliakivskamariana increasedsusceptibilityofhumanendothelialcellstoinfectionsbysarscov2variants AT luxanguillermo increasedsusceptibilityofhumanendothelialcellstoinfectionsbysarscov2variants AT nicinluka increasedsusceptibilityofhumanendothelialcellstoinfectionsbysarscov2variants AT aslangalips increasedsusceptibilityofhumanendothelialcellstoinfectionsbysarscov2variants AT miltinghendrik increasedsusceptibilityofhumanendothelialcellstoinfectionsbysarscov2variants AT kandlerjoshuad increasedsusceptibilityofhumanendothelialcellstoinfectionsbysarscov2variants AT dendorferandreas increasedsusceptibilityofhumanendothelialcellstoinfectionsbysarscov2variants AT heumuellerandreasw increasedsusceptibilityofhumanendothelialcellstoinfectionsbysarscov2variants AT flemingingrid increasedsusceptibilityofhumanendothelialcellstoinfectionsbysarscov2variants AT biblisofiairis increasedsusceptibilityofhumanendothelialcellstoinfectionsbysarscov2variants AT jakobitobias increasedsusceptibilityofhumanendothelialcellstoinfectionsbysarscov2variants AT dieterichchristoph increasedsusceptibilityofhumanendothelialcellstoinfectionsbysarscov2variants AT zeiherandreasm increasedsusceptibilityofhumanendothelialcellstoinfectionsbysarscov2variants AT cieseksandra increasedsusceptibilityofhumanendothelialcellstoinfectionsbysarscov2variants AT cinatljindrich increasedsusceptibilityofhumanendothelialcellstoinfectionsbysarscov2variants AT dimmelerstefanie increasedsusceptibilityofhumanendothelialcellstoinfectionsbysarscov2variants |