English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

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

Wagner, J. U. G., Bojkova, D., Shumliakivska, M., Luxan, G., Nicin, L., Aslan, G. S., et al. (2021). Increased susceptibility of human endothelial cells to infections by SARS-CoV-2 variants. BASIC RESEARCH IN CARDIOLOGY, 116(1): 42. doi:10.1007/s00395-021-00882-8.

Item is

Basic

show hide
Genre: Journal Article

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Wagner, Julian U. G., Author
Bojkova, Denisa, Author
Shumliakivska, Mariana, Author
Luxan, Guillermo, Author
Nicin, Luka, Author
Aslan, Galip S.1, Author              
Milting, Hendrik, Author
Kandler, Joshua D., Author
Dendorfer, Andreas, Author
Heumueller, Andreas W., Author
Fleming, Ingrid, Author
Bibli, Sofia-Iris, Author
Jakobi, Tobias, Author
Dieterich, Christoph, Author
Zeiher, Andreas M., Author
Ciesek, Sandra, Author
Cinatl, Jindrich, Author
Dimmeler, Stefanie, Author
Affiliations:
1IMPRS, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_3242057              

Content

show
hide
Free keywords: EXPRESSION; ACE2Cardiovascular System & Cardiology; Endothelial cells; SARS-CoV-2; Virus trapping; ER stress;
 Abstract: 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.

Details

show
hide
Language(s): eng - English
 Dates: 2021-07-05
 Publication Status: Published online
 Pages: 12
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000688277700001
DOI: 10.1007/s00395-021-00882-8
PMID: 34224022
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: BASIC RESEARCH IN CARDIOLOGY
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY : SPRINGER HEIDELBERG
Pages: - Volume / Issue: 116 (1) Sequence Number: 42 Start / End Page: - Identifier: ISSN: 0300-8428