Brain exposure to SARS-CoV-2 virions perturbs synaptic homeostasis.
Fiche publication
Date publication
mars 2024
Journal
Nature microbiology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr LABROUSSE Marc, Dr CARAPITO Christine
Tous les auteurs :
Partiot E, Hirschler A, Colomb S, Lutz W, Claeys T, Delalande F, Deffieu MS, Bare Y, Roels JRE, Gorda B, Bons J, Callon D, Andreoletti L, Labrousse M, Jacobs FMJ, Rigau V, Charlot B, Martens L, Carapito C, Ganesh G, Gaudin R
Lien Pubmed
Résumé
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with short- and long-term neurological complications. The variety of symptoms makes it difficult to unravel molecular mechanisms underlying neurological sequalae after coronavirus disease 2019 (COVID-19). Here we show that SARS-CoV-2 triggers the up-regulation of synaptic components and perturbs local electrical field potential. Using cerebral organoids, organotypic culture of human brain explants from individuals without COVID-19 and post-mortem brain samples from individuals with COVID-19, we find that neural cells are permissive to SARS-CoV-2 to a low extent. SARS-CoV-2 induces aberrant presynaptic morphology and increases expression of the synaptic components Bassoon, latrophilin-3 (LPHN3) and fibronectin leucine-rich transmembrane protein-3 (FLRT3). Furthermore, we find that LPHN3-agonist treatment with Stachel partially restored organoid electrical activity and reverted SARS-CoV-2-induced aberrant presynaptic morphology. Finally, we observe accumulation of relatively static virions at LPHN3-FLRT3 synapses, suggesting that local hindrance can contribute to synaptic perturbations. Together, our study provides molecular insights into SARS-CoV-2-brain interactions, which may contribute to COVID-19-related neurological disorders.
Référence
Nat Microbiol. 2024 03 28;: