期刊
STEM CELL REPORTS
卷 17, 期 2, 页码 307-320出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2021.12.011
关键词
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资金
- German Federal Ministry of Educa-tion and Research (Bundesministerium fudr Bildung und For-schung, BMBF) [01EK1608A, 01EK1608B, 01KX2021]
- internal Anti-Coronaprogram of the Fraunhofer-Gesell-schaft (DRECOR) [840260]
- internal Anti-Coronaprogram of the Fraunhofer-Gesell-schaft (iCARE) [602015]
- Deutsche Forschungsgemeinschaft [FR1720/18-1, GL589/10-1]
- Hamburg Ministry of Labour, Health, Family Affairs and Integration
- Nanostring
Neurological complications are common in COVID-19. This study reveals that SARS-CoV-2 can enter the brain through the blood-brain barrier and cause increased interferon signaling. In vitro experiments show that SARS-CoV-2 can infect BCECs and replicate, with the virus being transported across the barrier. This process can be inhibited by specific antibodies or inhibitors.
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.
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