Cargando…

Penetration of the SARS-CoV-2 Spike Protein across the Blood–Brain Barrier, as Revealed by a Combination of a Human Cell Culture Model System and Optical Biosensing

Since the outbreak of the global pandemic caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), several clinical aspects of the disease have come into attention. Besides its primary route of infection through the respiratory system, SARS-CoV-2 is known to have neuroinvasive capacity, causin...

Descripción completa

Detalles Bibliográficos
Autores principales: Petrovszki, Dániel, Walter, Fruzsina R., Vigh, Judit P., Kocsis, Anna, Valkai, Sándor, Deli, Mária A., Dér, András
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773803/
https://www.ncbi.nlm.nih.gov/pubmed/35052867
http://dx.doi.org/10.3390/biomedicines10010188
_version_ 1784636187034517504
author Petrovszki, Dániel
Walter, Fruzsina R.
Vigh, Judit P.
Kocsis, Anna
Valkai, Sándor
Deli, Mária A.
Dér, András
author_facet Petrovszki, Dániel
Walter, Fruzsina R.
Vigh, Judit P.
Kocsis, Anna
Valkai, Sándor
Deli, Mária A.
Dér, András
author_sort Petrovszki, Dániel
collection PubMed
description Since the outbreak of the global pandemic caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), several clinical aspects of the disease have come into attention. Besides its primary route of infection through the respiratory system, SARS-CoV-2 is known to have neuroinvasive capacity, causing multiple neurological symptoms with increased neuroinflammation and blood–brain barrier (BBB) damage. The viral spike protein disseminates via circulation during infection, and when reaching the brain could possibly cross the BBB, which was demonstrated in mice. Therefore, its medical relevance is of high importance. The aim of this study was to evaluate the barrier penetration of the S1 subunit of spike protein in model systems of human organs highly exposed to the infection. For this purpose, in vitro human BBB and intestinal barrier cell–culture systems were investigated by an optical biosensing method. We found that spike protein crossed the human brain endothelial cell barrier effectively. Additionally, spike protein passage was found in a lower amount for the intestinal barrier cell layer. These observations were corroborated with parallel specific ELISAs. The findings on the BBB model could provide a further basis for studies focusing on the mechanism and consequences of spike protein penetration across the BBB to the brain.
format Online
Article
Text
id pubmed-8773803
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-87738032022-01-21 Penetration of the SARS-CoV-2 Spike Protein across the Blood–Brain Barrier, as Revealed by a Combination of a Human Cell Culture Model System and Optical Biosensing Petrovszki, Dániel Walter, Fruzsina R. Vigh, Judit P. Kocsis, Anna Valkai, Sándor Deli, Mária A. Dér, András Biomedicines Article Since the outbreak of the global pandemic caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), several clinical aspects of the disease have come into attention. Besides its primary route of infection through the respiratory system, SARS-CoV-2 is known to have neuroinvasive capacity, causing multiple neurological symptoms with increased neuroinflammation and blood–brain barrier (BBB) damage. The viral spike protein disseminates via circulation during infection, and when reaching the brain could possibly cross the BBB, which was demonstrated in mice. Therefore, its medical relevance is of high importance. The aim of this study was to evaluate the barrier penetration of the S1 subunit of spike protein in model systems of human organs highly exposed to the infection. For this purpose, in vitro human BBB and intestinal barrier cell–culture systems were investigated by an optical biosensing method. We found that spike protein crossed the human brain endothelial cell barrier effectively. Additionally, spike protein passage was found in a lower amount for the intestinal barrier cell layer. These observations were corroborated with parallel specific ELISAs. The findings on the BBB model could provide a further basis for studies focusing on the mechanism and consequences of spike protein penetration across the BBB to the brain. MDPI 2022-01-17 /pmc/articles/PMC8773803/ /pubmed/35052867 http://dx.doi.org/10.3390/biomedicines10010188 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Petrovszki, Dániel
Walter, Fruzsina R.
Vigh, Judit P.
Kocsis, Anna
Valkai, Sándor
Deli, Mária A.
Dér, András
Penetration of the SARS-CoV-2 Spike Protein across the Blood–Brain Barrier, as Revealed by a Combination of a Human Cell Culture Model System and Optical Biosensing
title Penetration of the SARS-CoV-2 Spike Protein across the Blood–Brain Barrier, as Revealed by a Combination of a Human Cell Culture Model System and Optical Biosensing
title_full Penetration of the SARS-CoV-2 Spike Protein across the Blood–Brain Barrier, as Revealed by a Combination of a Human Cell Culture Model System and Optical Biosensing
title_fullStr Penetration of the SARS-CoV-2 Spike Protein across the Blood–Brain Barrier, as Revealed by a Combination of a Human Cell Culture Model System and Optical Biosensing
title_full_unstemmed Penetration of the SARS-CoV-2 Spike Protein across the Blood–Brain Barrier, as Revealed by a Combination of a Human Cell Culture Model System and Optical Biosensing
title_short Penetration of the SARS-CoV-2 Spike Protein across the Blood–Brain Barrier, as Revealed by a Combination of a Human Cell Culture Model System and Optical Biosensing
title_sort penetration of the sars-cov-2 spike protein across the blood–brain barrier, as revealed by a combination of a human cell culture model system and optical biosensing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773803/
https://www.ncbi.nlm.nih.gov/pubmed/35052867
http://dx.doi.org/10.3390/biomedicines10010188
work_keys_str_mv AT petrovszkidaniel penetrationofthesarscov2spikeproteinacrossthebloodbrainbarrierasrevealedbyacombinationofahumancellculturemodelsystemandopticalbiosensing
AT walterfruzsinar penetrationofthesarscov2spikeproteinacrossthebloodbrainbarrierasrevealedbyacombinationofahumancellculturemodelsystemandopticalbiosensing
AT vighjuditp penetrationofthesarscov2spikeproteinacrossthebloodbrainbarrierasrevealedbyacombinationofahumancellculturemodelsystemandopticalbiosensing
AT kocsisanna penetrationofthesarscov2spikeproteinacrossthebloodbrainbarrierasrevealedbyacombinationofahumancellculturemodelsystemandopticalbiosensing
AT valkaisandor penetrationofthesarscov2spikeproteinacrossthebloodbrainbarrierasrevealedbyacombinationofahumancellculturemodelsystemandopticalbiosensing
AT delimariaa penetrationofthesarscov2spikeproteinacrossthebloodbrainbarrierasrevealedbyacombinationofahumancellculturemodelsystemandopticalbiosensing
AT derandras penetrationofthesarscov2spikeproteinacrossthebloodbrainbarrierasrevealedbyacombinationofahumancellculturemodelsystemandopticalbiosensing