SARS-CoV-2 infects epithelial cells of the blood-cerebrospinal fluid barrier rather than endothelial cells or pericytes of the blood-brain barrier

• Verfasst von: Stüdle, Chiara [VerfasserIn]
• Verfasst von: Nishihara, Hideaki [VerfasserIn]
• Verfasst von: Wischnewski, Sven [VerfasserIn]
• Verfasst von: Kulsvehagen, Laila [VerfasserIn]
• Verfasst von: Perriot, Sylvain [VerfasserIn]
• Verfasst von: Ishikawa, Hiroshi [VerfasserIn]
• Verfasst von: Schroten, Horst [VerfasserIn]
• Verfasst von: Frank, Stephan [VerfasserIn]
• Verfasst von: Deigendesch, Nikolaus [VerfasserIn]
• Verfasst von: Du Pasquier, Renaud [VerfasserIn]
• Verfasst von: Schirmer, Lucas [VerfasserIn]
• Verfasst von: Pröbstel, Anne-Katrin [VerfasserIn]
• Verfasst von: Engelhardt, Britta [VerfasserIn]
• Titel: SARS-CoV-2 infects epithelial cells of the blood-cerebrospinal fluid barrier rather than endothelial cells or pericytes of the blood-brain barrier
• Verf.angabe: Chiara Stüdle, Hideaki Nishihara, Sven Wischnewski, Laila Kulsvehagen, Sylvain Perriot, Hiroshi Ishikawa, Horst Schroten, Stephan Frank, Nikolaus Deigendesch, Renaud Du Pasquier, Lucas Schirmer, Anne-Katrin Pröbstel and Britta Engelhardt
• E-Jahr: 2023
• Jahr: 24 October 2023
• Umfang: 21 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 22.07.2024
• Titel Quelle: Enthalten in: Fluids and barriers of the CNS
• Ort Quelle: London : BioMed Central, 2011
• Jahr Quelle: 2023
• Band/Heft Quelle: 20(2023), 1 vom: Okt., Seite 1-21
• ISSN Quelle: 2045-8118
• DOI: doi:10.1186/s12987-023-00479-4
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1895999111

Abstract

As a consequence of SARS-CoV-2 infection various neurocognitive and neuropsychiatric symptoms can appear, which may persist for several months post infection. However, cell type-specific routes of brain infection and underlying mechanisms resulting in neuroglial dysfunction are not well understood. Here, we investigated the susceptibility of cells constituting the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus (ChP) to SARS-CoV-2 infection using human induced pluripotent stem cell (hiPSC)-derived cellular models and a ChP papilloma-derived epithelial cell line as well as ChP tissue from COVID-19 patients, respectively. We noted a differential infectibility of hiPSC-derived brain microvascular endothelial cells (BMECs) depending on the differentiation method. Extended endothelial culture method (EECM)-BMECs characterized by a complete set of endothelial markers, good barrier properties and a mature immune phenotype were refractory to SARS-CoV-2 infection and did not exhibit an activated phenotype after prolonged SARS-CoV-2 inoculation. In contrast, defined medium method (DMM)-BMECs, characterized by a mixed endothelial and epithelial phenotype and excellent barrier properties were productively infected by SARS-CoV-2 in an ACE2-dependent manner. hiPSC-derived brain pericyte-like cells (BPLCs) lacking ACE2 expression were not susceptible to SARS-CoV-2 infection. Furthermore, the human choroid plexus papilloma-derived epithelial cell line HIBCPP, modeling the BCSFB was productively infected by SARS-CoV-2 preferentially from the basolateral side, facing the blood compartment. Assessment of ChP tissue from COVID-19 patients by RNA in situ hybridization revealed SARS-CoV-2 transcripts in ChP epithelial and ChP stromal cells. Our study shows that the BCSFB of the ChP rather than the BBB is susceptible to direct SARS-CoV-2 infection. Thus, neuropsychiatric symptoms because of COVID-19 may rather be associated with dysfunction of the BCSFB than the BBB. Future studies should consider a role of the ChP in underlying neuropsychiatric symptoms following SARS-CoV-2 infection.