The blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-2.
Stem Cell Reports
; 17(2): 307-320, 2022 02 08.
Artigo
em Inglês
| MEDLINE | ID: covidwho-1712991
ABSTRACT
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.
Palavras-chave
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
MEDLINE
Assunto principal:
Barreira Hematoencefálica
/
Sistema Nervoso Central
/
Internalização do Vírus
/
SARS-CoV-2
Limite:
Humanos
Idioma:
Inglês
Revista:
Stem Cell Reports
Ano de publicação:
2022
Tipo de documento:
Artigo
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