Trans-synaptic dwelling of SARS-CoV-2 particles perturbs neural synapse organization and function

Partiot, E.; Hirschler, A.; Colomb, S.; Lutz, W.; Claeys, T.; Delalande, F.; Deffieu, M. S.; Roels, J.; Bons, J.; Callon, D.; Andreoletti, L.; Labrousse, M.; Jacobs, F. M.; Rigau, V.; Charlot, B.; Martens, L.; Carapito, C.; Ganesh, G.; Gaudin, R.

doi:10.1101/2022.09.13.507484

bioRxiv · 10.1101/2022.09.13.507484

Trans-synaptic dwelling of SARS-CoV-2 particles perturbs neural synapse organization and function

Partiot, E.·Hirschler, A.·Colomb, S.·Lutz, W.·Claeys, T.·Delalande, F.·Deffieu, M. S.·Roels, J.·Bons, J.·Callon, D.·Andreoletti, L.·Labrousse, M.·Jacobs, F. M.·Rigau, V.·Charlot, B.·Martens, L.·Carapito, C.·Ganesh, G.·Gaudin, R.

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Abstract

SARS-CoV-2 infection is associated with short- and long-term neurological and psychiatric complications, referred to as neuroCOVID. These symptoms are relatively heterogenous and fluctuating, hampering the discovery of molecular mechanisms underlying viro-induced brain perturbations. Here, we show that the human cerebral cortex poorly supports SARS-CoV-2 dissemination using post-mortem COVID-19 patient samples, ex vivo organotypic cultures of human brain explants and stem cell-derived cortical organoids. Despite restricted infection, the sole exposure of neural cells to SARS-CoV-2 particles is sufficient to induce significant perturbations on neural synapse organization associated to electrical activity dysfunction. Single-organoid proteomics revealed that exposure to SARS-CoV-2 is associated to trans-synaptic proteins upregulation and unveiled that incoming virions dwell at LPHN3/FLRT3-containing synapses. Our study provides new mechanistic insights on the origin of SARS-CoV-2-induced neurological disorders. One-Sentence SummarySARS-CoV-2 modulates neural plasticity and electrical activity as viral particles lodge at the trans-synaptic interface.

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Partiot, E., Hirschler, A., Colomb, S., Lutz, W., Claeys, T., Delalande, F., Deffieu, M. S., Roels, J., Bons, J., Callon, D., Andreoletti, L., Labrousse, M., Jacobs, F. M., Rigau, V., Charlot, B., Martens, L., Carapito, C., Ganesh, G., Gaudin, R.. 2022-09-14. Trans-synaptic dwelling of SARS-CoV-2 particles perturbs neural synapse organization and function. https://doi.org/10.1101/2022.09.13.507484

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