J Virol . 2 SARS-CoV-2 causes severe epithelial inflammation and barrier dysfunction

[tetano]

J Virol


. 2021 Feb 26;JVI.00110-21.
doi: 10.1128/JVI.00110-21. Online ahead of print.
SARS-CoV-2 causes severe epithelial inflammation and barrier dysfunction


Stefanie Deinhardt-Emmer[SUP] 1 [/SUP], Sarah B?ttcher[SUP] 2 [/SUP], Clio H?ring[SUP] 2 [/SUP], Liane Giebeler[SUP] 2 [/SUP], Andreas Henke[SUP] 2 [/SUP], Roland Zell[SUP] 2 [/SUP], Johannes Jungwirth[SUP] 2 [/SUP], Paul M Jordan[SUP] 3 [/SUP], Oliver Werz[SUP] 3 [/SUP], Franziska Hornung[SUP] 4 [/SUP], Christian Brandt[SUP] 5 [/SUP], Mike Marquet[SUP] 5 [/SUP], Alexander S Mosig[SUP] 6 [/SUP], Mathias W Pletz[SUP] 5 [/SUP], Michael Schacke[SUP] 2 [/SUP], J?rgen R?del[SUP] 4 [/SUP], Regine Heller[SUP] 7 [/SUP], Sandor Nietzsche[SUP] 8 [/SUP], Bettina L?ffler[SUP] 4 [/SUP], Christina Ehrhardt[SUP] 9 [/SUP]



Affiliations

• PMID: 33637603
• DOI: 10.1128/JVI.00110-21

Abstract

Infections with 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. By 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 was 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 the damage of the epithelial/endothelial barrier function and viral dissemination.

IMPORTANCE

SARS-CoV-2 challenges healthcare 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. 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.

 

[sharon sanders]

Epithelial Tissue


Epithelial tissues are widespread throughout the body. They form the covering of all body surfaces, line body cavities and hollow organs, and are the major tissue in glands. They perform a variety of functions that include protection, secretion, absorption, excretion, filtration, diffusion, and sensory reception.

The cells in epithelial tissue are tightly packed together with very little intercellular matrix. Because the tissues form coverings and linings, the cells have one free surface that is not in contact with other cells. Opposite the free surface, the cells are attached to underlying connective tissue by a non-cellular basement membrane. This membrane is a mixture of carbohydrates and proteins secreted by the epithelial and connective tissue cells.

Epithelial cells may be squamous, cuboidal, or columnar in shape and may be arranged in single or multiple layers.

Simple cuboidal epithelium is found in glandular tissue and in the kidney tubules. Simple columnar epithelium lines the stomach and intestines. Pseudostratified columnar epithelium lines portions of the respiratory tract and some of the tubes of the male reproductive tract. Transitional epithelium can be distended or stretched. Glandular epithelium is specialized to produce and secrete substances.


https://training.seer.cancer.gov/anatomy/cells_tissues_membranes/tissues/epithelial.html

 

[sharon sanders]

Endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels, and lymphatic vessels.[SUP][1][/SUP] The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. Endothelial cells form the barrier between vessels and tissue and control the flow of substances and fluid into and out of a tissue.

Endothelial cells in direct contact with blood are called vascular endothelial cells whereas those in direct contact with lymph are known as lymphatic endothelial cells. Vascular endothelial cells line the entire circulatory system, from the heart to the smallest capillaries.

https://en.wikipedia.org/wiki/Endothelium