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Stüdle, Chiara [Author]; Nishihara, Hideaki [Author]; Wischnewski, Sven [Author]; Kulsvehagen, Laila [Author]; Perriot, Sylvain [Author]; Ishikawa, Hiroshi [Author]; Schroten, Horst [Author]; Frank, Stephan [Author]; Deigendesch, Nikolaus [Author]; Du Pasquier, Renaud [Author]; Schirmer, Lucas [Author]; Pröbstel, Anne-Katrin [Author]; Engelhardt, Britta [Author]

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

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  • Media type: E-Article
  • Title: SARS-CoV-2 infects epithelial cells of the blood-cerebrospinal fluid barrier rather than endothelial cells or pericytes of the blood-brain barrier
  • Contributor: Stüdle, Chiara [Author]; Nishihara, Hideaki [Author]; Wischnewski, Sven [Author]; Kulsvehagen, Laila [Author]; Perriot, Sylvain [Author]; Ishikawa, Hiroshi [Author]; Schroten, Horst [Author]; Frank, Stephan [Author]; Deigendesch, Nikolaus [Author]; Du Pasquier, Renaud [Author]; Schirmer, Lucas [Author]; Pröbstel, Anne-Katrin [Author]; Engelhardt, Britta [Author]
  • Published: 24 October 2023
  • Published in: Fluids and barriers of the CNS ; 20(2023), 1 vom: Okt., Seite 1-21
  • Language: English
  • DOI: 10.1186/s12987-023-00479-4
  • Identifier:
  • Origination:
  • Footnote:
  • Description: 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.
  • Access State: Open Access