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Cytoskeletal ß-tubulin and cysteine cathepsin L deregulation by SARS-CoV-2 spike protein interaction with the neuronal model cell line SH-SY5Y.
Oliveira, Bernardo R; Nehlmeier, Inga; Kempf, Amy Madeleine; Venugopalan, Vaishnavi; Rehders, Maren; Ceniza, Marianne E P; Cavalcanti, Pedro A de T P V; Hoffmann, Markus; Pöhlmann, Stefan; Brix, Klaudia.
Afiliación
  • Oliveira BR; Constructor University, School of Science, Campus Ring 1, D-28759, Bremen, Germany.
  • Nehlmeier I; Deutsches Primatenzentrum - Leibniz-Institut für Primatenforschung, Abteilung Infektionsbiologie, Kellnerweg 4, D-37077, Göttingen, Germany. Electronic address: INehlmeier@dpz.eu.
  • Kempf AM; Deutsches Primatenzentrum - Leibniz-Institut für Primatenforschung, Abteilung Infektionsbiologie, Kellnerweg 4, D-37077, Göttingen, Germany; Faculty of Biology and Psychology, Georg-August University Göttingen, Wilhelmsplatz 1, D-37073, Göttingen, Germany. Electronic address: AKempf@dpz.eu.
  • Venugopalan V; Constructor University, School of Science, Campus Ring 1, D-28759, Bremen, Germany.
  • Rehders M; Constructor University, School of Science, Campus Ring 1, D-28759, Bremen, Germany. Electronic address: mrehders@constructor.university.
  • Ceniza MEP; Constructor University, School of Science, Campus Ring 1, D-28759, Bremen, Germany. Electronic address: mceniza@constructor.university.
  • Cavalcanti PATPV; Constructor University, School of Science, Campus Ring 1, D-28759, Bremen, Germany. Electronic address: pcavalcanti@constructor.university.
  • Hoffmann M; Deutsches Primatenzentrum - Leibniz-Institut für Primatenforschung, Abteilung Infektionsbiologie, Kellnerweg 4, D-37077, Göttingen, Germany; Faculty of Biology and Psychology, Georg-August University Göttingen, Wilhelmsplatz 1, D-37073, Göttingen, Germany. Electronic address: MHoffmann@dpz.eu.
  • Pöhlmann S; Deutsches Primatenzentrum - Leibniz-Institut für Primatenforschung, Abteilung Infektionsbiologie, Kellnerweg 4, D-37077, Göttingen, Germany; Faculty of Biology and Psychology, Georg-August University Göttingen, Wilhelmsplatz 1, D-37073, Göttingen, Germany. Electronic address: SPoehlmann@dpz.eu.
  • Brix K; Constructor University, School of Science, Campus Ring 1, D-28759, Bremen, Germany. Electronic address: kbrix@constructor.university.
Biochimie ; 2024 Mar 01.
Article en En | MEDLINE | ID: mdl-38432290
ABSTRACT
SARS-CoV-2 mainly infects the respiratory tract but can also target other organs, including the central nervous system. While it was recently shown that cells of the blood-brain-barrier are permissive to SARS-CoV-2 infection in vitro, it remains debated whether neurons can be infected. In this study, we demonstrate that vesicular stomatitis virus particles pseudotyped with the spike protein of SARS-CoV-2 variants WT, Alpha, Delta and Omicron enter the neuronal model cell line SH-SY5Y. Cell biological analyses of the pseudo-virus treated cultures showed marked alterations in microtubules of SH-SY5Y cells. Because the changes in ß-tubulin occurred in most cells, but only few were infected, we further asked whether interaction of the cells with spike protein might be sufficient to cause molecular and structural changes. For this, SH-SY5Y cells were incubated with trimeric spike proteins for time intervals of up to 24 h. CellProfiler™-based image analyses revealed changes in the intensities of microtubule staining in spike protein-incubated cells. Furthermore, expression of the spike protein-processing protease cathepsin L was found to be up-regulated by wild type, Alpha and Delta spike protein pseudotypes and cathepsin L was found to be secreted from spike protein-treated cells. We conclude that the mere interaction of the SARS-CoV-2 with neuronal cells can affect cellular architecture and proteolytic capacities. The molecular mechanisms underlying SARS-CoV-2 spike protein induced cytoskeletal changes in neuronal cells remain elusive and require future studies.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: Biochimie Año: 2024 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: Biochimie Año: 2024 Tipo del documento: Article País de afiliación: Alemania