Brain exposure to SARS-CoV-2 virions perturbs synaptic homeostasis.
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
28 Mar 2024
28 Mar 2024
Historique:
received:
06
04
2023
accepted:
04
03
2024
pubmed:
29
3
2024
medline:
29
3
2024
entrez:
29
3
2024
Statut:
aheadofprint
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.
Identifiants
pubmed: 38548923
doi: 10.1038/s41564-024-01657-2
pii: 10.1038/s41564-024-01657-2
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-21-CE33-0007-03
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-22-CE15-0007-01
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-10-INBS-08-03; ProFI FR2048
Organisme : Fondation pour la Recherche Médicale (Foundation for Medical Research in France)
ID : MIE202207016212
Organisme : Fondation pour la Recherche Médicale (Foundation for Medical Research in France)
ID : SPF202110014043
Organisme : Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)
ID : 1S57123N
Organisme : Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)
ID : G028821N
Organisme : Universitair Ziekenhuis Gent (Ghent University Hospital)
ID : BOF21/GOA/033
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : H2020-INFRAIA-2018-1
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature Limited.
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