Résumé
The utility of human neuroblastoma cell lines as in vitro model to study neuro-invasiveness and neuro-virulence of SARS-CoV-2 has been demonstrated by our laboratory and others. The aim of this report is to further characterize the associated cellular responses caused by a pre-alpha SARS-CoV-2 strain on differentiated SH-SY5Y and to prevent its cytopathic effect by using a set of entry inhibitors. The susceptibility of SH-SY5Y to SARS-CoV-2 was confirmed at high multiplicity-of-infection, without viral replication or release. Infection caused a reduction in the length of neuritic processes, occurrence of plasma membrane blebs, cell clustering, and changes in lipid droplets electron density. No changes in the expression of cytoskeletal proteins, such as tubulins or tau, could explain neurite shortening. To counteract the toxic effect on neurites, entry inhibitors targeting TMPRSS2, ACE2, NRP1 receptors, and Spike RBD were co-incubated with the viral inoculum. The neurite shortening could be prevented by the highest concentration of camostat mesylate, anti-RBD antibody, and NRP1 inhibitor, but not by soluble ACE2. According to the degree of entry inhibition, the average amount of intracellular viral RNA was negatively correlated to neurite length. This study demonstrated that targeting specific SARS-CoV-2 host receptors could reverse its neurocytopathic effect on SH-SY5Y.
langue originale | Anglais |
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Numéro d'article | 2020 |
journal | Viruses |
Volume | 15 |
Numéro de publication | 10 |
Les DOIs | |
Etat de la publication | Publié - oct. 2023 |
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Laboratoire de sécurité biologique au niveau 3 (BL3)
De Bolle, X. (!!Manager)
Plateforme technologique Laboratoire de securite biologique au niveau 3Equipement/installations: Plateforme technolgique
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Microscopie électronique
Colomer, J.-F. (!!Manager) & Charlier, C. (!!Operator)
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Microscopie optique
Renard, H.-F. (!!Manager), Forrester, A. (!!Manager), Demazy, C. (!!Other) & Ledoux, B. (!!Manager)
Plateforme technologique Morphologie, imagerieEquipement/installations: Equipement
Presse/médias
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New Findings Reported from Universite de Namur Describe Advances in COVID-19 (Viral Entry Inhibitors Protect against SARS-CoV-2-Induced Neurite Shortening in Differentiated SH-SY5Y Cells)
Nicaise, C., GILLOTEAUX, J., Bielarz, V., De Swert, K. & Gillet, N.
9/11/23
1 élément de Couverture média
Presse/Médias: Commentaire d'expert
Ensembles de données
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Viral entry inhibitors protect against SARS-CoV-2-induced neurite shortening in differentiated SH-SY5Y cells
Nicaise, C. (Créateur), MIGNOLET, M. (Créateur), GILLOTEAUX, J. (Créateur) & Gueibe, M. (Créateur), University of Namur, 24 août 2023
Ensemble de données