The blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-2
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The blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-2. / Krasemann, Susanne; Haferkamp, Undine; Pfefferle, Susanne; Woo, Marcel S; Heinrich, Fabian; Schweizer, Michaela; Appelt-Menzel, Antje; Cubukova, Alevtina; Barenberg, Janica; Leu, Jennifer; Hartmann, Kristin; Thies, Edda; Littau, Jessica Lisa; Sepulveda-Falla, Diego; Zhang, Liang; Ton, Kathy; Liang, Yan; Matschke, Jakob; Ricklefs, Franz; Sauvigny, Thomas; Sperhake, Jan; Fitzek, Antonia; Gerhartl, Anna; Brachner, Andreas; Geiger, Nina; König, Eva-Maria; Bodem, Jochen; Franzenburg, Sören; Franke, Andre; Moese, Stefan; Müller, Franz-Josef; Geisslinger, Gerd; Claussen, Carsten; Kannt, Aimo; Zaliani, Andrea; Gribbon, Philip; Ondruschka, Benjamin; Neuhaus, Winfried; Friese, Manuel A; Glatzel, Markus; Pless, Ole.
in: STEM CELL REP, Jahrgang 17, Nr. 2, 08.02.2022, S. 307-320.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - The blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-2
AU - Krasemann, Susanne
AU - Haferkamp, Undine
AU - Pfefferle, Susanne
AU - Woo, Marcel S
AU - Heinrich, Fabian
AU - Schweizer, Michaela
AU - Appelt-Menzel, Antje
AU - Cubukova, Alevtina
AU - Barenberg, Janica
AU - Leu, Jennifer
AU - Hartmann, Kristin
AU - Thies, Edda
AU - Littau, Jessica Lisa
AU - Sepulveda-Falla, Diego
AU - Zhang, Liang
AU - Ton, Kathy
AU - Liang, Yan
AU - Matschke, Jakob
AU - Ricklefs, Franz
AU - Sauvigny, Thomas
AU - Sperhake, Jan
AU - Fitzek, Antonia
AU - Gerhartl, Anna
AU - Brachner, Andreas
AU - Geiger, Nina
AU - König, Eva-Maria
AU - Bodem, Jochen
AU - Franzenburg, Sören
AU - Franke, Andre
AU - Moese, Stefan
AU - Müller, Franz-Josef
AU - Geisslinger, Gerd
AU - Claussen, Carsten
AU - Kannt, Aimo
AU - Zaliani, Andrea
AU - Gribbon, Philip
AU - Ondruschka, Benjamin
AU - Neuhaus, Winfried
AU - Friese, Manuel A
AU - Glatzel, Markus
AU - Pless, Ole
N1 - Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2022/2/8
Y1 - 2022/2/8
N2 - Neurological complications are common in COVID-19. Although SARS-CoV-2 has been detected in patients' brain tissues, its entry routes and resulting consequences are not well understood. Here, we show a pronounced upregulation of interferon signaling pathways of the neurovascular unit in fatal COVID-19. By investigating the susceptibility of human induced pluripotent stem cell (hiPSC)-derived brain capillary endothelial-like cells (BCECs) to SARS-CoV-2 infection, we found that BCECs were infected and recapitulated transcriptional changes detected in vivo. While BCECs were not compromised in their paracellular tightness, we found SARS-CoV-2 in the basolateral compartment in transwell assays after apical infection, suggesting active replication and transcellular transport of virus across the blood-brain barrier (BBB) in vitro. Moreover, entry of SARS-CoV-2 into BCECs could be reduced by anti-spike-, anti-angiotensin-converting enzyme 2 (ACE2)-, and anti-neuropilin-1 (NRP1)-specific antibodies or the transmembrane protease serine subtype 2 (TMPRSS2) inhibitor nafamostat. Together, our data provide strong support for SARS-CoV-2 brain entry across the BBB resulting in increased interferon signaling.
AB - Neurological complications are common in COVID-19. Although SARS-CoV-2 has been detected in patients' brain tissues, its entry routes and resulting consequences are not well understood. Here, we show a pronounced upregulation of interferon signaling pathways of the neurovascular unit in fatal COVID-19. By investigating the susceptibility of human induced pluripotent stem cell (hiPSC)-derived brain capillary endothelial-like cells (BCECs) to SARS-CoV-2 infection, we found that BCECs were infected and recapitulated transcriptional changes detected in vivo. While BCECs were not compromised in their paracellular tightness, we found SARS-CoV-2 in the basolateral compartment in transwell assays after apical infection, suggesting active replication and transcellular transport of virus across the blood-brain barrier (BBB) in vitro. Moreover, entry of SARS-CoV-2 into BCECs could be reduced by anti-spike-, anti-angiotensin-converting enzyme 2 (ACE2)-, and anti-neuropilin-1 (NRP1)-specific antibodies or the transmembrane protease serine subtype 2 (TMPRSS2) inhibitor nafamostat. Together, our data provide strong support for SARS-CoV-2 brain entry across the BBB resulting in increased interferon signaling.
U2 - 10.1016/j.stemcr.2021.12.011
DO - 10.1016/j.stemcr.2021.12.011
M3 - SCORING: Journal article
C2 - 35063125
VL - 17
SP - 307
EP - 320
JO - STEM CELL REP
JF - STEM CELL REP
SN - 2213-6711
IS - 2
ER -