Increased susceptibility of human endothelial cells to infections by SARS-CoV-2 variants

  1. Wagner, Julian U. G.
  2. Bojkova, Denisa
  3. Shumliakivska, Mariana
  4. Luxán, Guillermo ORCID logo
  5. Nicin, Luka
  6. Aslan, Galip S.
  7. Milting, Hendrik
  8. Kandler, Joshua D.
  9. Dendorfer, Andreas
  10. Heumueller, Andreas W.
  11. Fleming, Ingrid
  12. Bibli, Sofia-Iris
  13. Jakobi, Tobias
  14. Dieterich, Christoph
  15. Zeiher, Andreas M.
  16. Ciesek, Sandra
  17. Cinatl, Jindrich
  18. Dimmeler, Stefanie ORCID logo

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1000 Titel
  • Increased susceptibility of human endothelial cells to infections by SARS-CoV-2 variants
1000 Autor/in
  1. Wagner, Julian U. G. |
  2. Bojkova, Denisa |
  3. Shumliakivska, Mariana |
  4. Luxán, Guillermo |
  5. Nicin, Luka |
  6. Aslan, Galip S. |
  7. Milting, Hendrik |
  8. Kandler, Joshua D. |
  9. Dendorfer, Andreas |
  10. Heumueller, Andreas W. |
  11. Fleming, Ingrid |
  12. Bibli, Sofia-Iris |
  13. Jakobi, Tobias |
  14. Dieterich, Christoph |
  15. Zeiher, Andreas M. |
  16. Ciesek, Sandra |
  17. Cinatl, Jindrich |
  18. Dimmeler, Stefanie |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-07-05
1000 Erschienen in
1000 Quellenangabe
  • 116(1):42
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00395-021-00882-8 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256413/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • 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.
1000 Sacherschließung
lokal Endothelial Cells/metabolism [MeSH]
lokal Calnexin/metabolism [MeSH]
lokal Endoplasmic Reticulum/metabolism [MeSH]
lokal SARS-CoV-2/pathogenicity [MeSH]
lokal Receptors, Virus/metabolism [MeSH]
lokal Humans [MeSH]
lokal Original Contribution
lokal SARS-CoV-2/genetics [MeSH]
lokal Host-Pathogen Interactions [MeSH]
lokal Virus trapping
lokal ER stress
lokal Endothelial Cells/virology [MeSH]
lokal Endothelial cells
lokal Membrane Proteins/metabolism [MeSH]
lokal Angiotensin-Converting Enzyme 2/metabolism [MeSH]
lokal Endoplasmic Reticulum/virology [MeSH]
lokal Cells, Cultured [MeSH]
lokal SARS-CoV-2/metabolism [MeSH]
lokal Spike Glycoprotein, Coronavirus/metabolism [MeSH]
lokal Endoplasmic Reticulum Stress [MeSH]
lokal SARS-CoV-2
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/V2FnbmVyLCBKdWxpYW4gVS4gRy4=|https://frl.publisso.de/adhoc/uri/Qm9qa292YSwgRGVuaXNh|https://frl.publisso.de/adhoc/uri/U2h1bWxpYWtpdnNrYSwgTWFyaWFuYQ==|https://orcid.org/0000-0001-8350-8659|https://frl.publisso.de/adhoc/uri/TmljaW4sIEx1a2E=|https://frl.publisso.de/adhoc/uri/QXNsYW4sIEdhbGlwIFMu|https://frl.publisso.de/adhoc/uri/TWlsdGluZywgSGVuZHJpaw==|https://frl.publisso.de/adhoc/uri/S2FuZGxlciwgSm9zaHVhIEQu|https://frl.publisso.de/adhoc/uri/RGVuZG9yZmVyLCBBbmRyZWFz|https://frl.publisso.de/adhoc/uri/SGV1bXVlbGxlciwgQW5kcmVhcyBXLg==|https://frl.publisso.de/adhoc/uri/RmxlbWluZywgSW5ncmlk|https://frl.publisso.de/adhoc/uri/QmlibGksIFNvZmlhLUlyaXM=|https://frl.publisso.de/adhoc/uri/SmFrb2JpLCBUb2JpYXM=|https://frl.publisso.de/adhoc/uri/RGlldGVyaWNoLCBDaHJpc3RvcGg=|https://frl.publisso.de/adhoc/uri/WmVpaGVyLCBBbmRyZWFzIE0u|https://frl.publisso.de/adhoc/uri/Q2llc2VrLCBTYW5kcmE=|https://frl.publisso.de/adhoc/uri/Q2luYXRsLCBKaW5kcmljaA==|https://orcid.org/0000-0002-1045-2436
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  • DeepGreen-ID: f4ba260117bb4c6a868408ccb1155476 ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
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1000 Erstellt am 2023-05-11T10:51:59.040+0200
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1000 Zuletzt bearbeitet 2023-10-21T03:58:18.299+0200
1000 Objekt bearb. Sat Oct 21 03:58:18 CEST 2023
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