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Tunneling nanotubes provide a novel route for SARS-CoV-2 spreading between permissive cells and to non-permissive neuronal cells

Abstract : SARS-CoV-2 entry into host cells is mediated by the binding of its spike glycoprotein to the angiotensin-converting enzyme 2 (ACE2) receptor, highly expressed in several organs, but very low in the brain. The mechanism through which SARS-CoV-2 infects neurons is not understood. Tunneling nanotubes (TNTs), actin-based intercellular conduits that connect distant cells, allow the transfer of cargos, including viruses. Here, we explored the neuroinvasive potential of SARS-CoV-2 and whether TNTs are involved in its spreading between cells in vitro. We report that neuronal cells, not permissive to SARS-CoV-2 through an exocytosis/endocytosis dependent pathway, can be infected when co-cultured with permissive infected epithelial cells. SARS-CoV-2 induces TNTs formation between permissive cells and exploits this route to spread to uninfected permissive cells in co-culture. Correlative Cryo-electron tomography reveals that SARS-CoV-2 is associated with the plasma membrane of TNTs formed between permissive cells and virus-like vesicular structures are inside TNTs established both between permissive cells and between permissive and non-permissive cells. Our data highlight a potential novel mechanism of SARS-CoV-2 spreading which could serve as route to invade non-permissive cells and potentiate infection in permissive cells.
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Preprints, Working Papers, ...
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03695860
Contributor : Reine BOUYSSIE Connect in order to contact the contributor
Submitted on : Wednesday, June 15, 2022 - 12:05:14 PM
Last modification on : Saturday, June 25, 2022 - 3:44:10 AM

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2021.11.15.468633v1.full.pdf
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Distributed under a Creative Commons Attribution - NonCommercial - NoDerivatives 4.0 International License

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Anna Pepe, Stefano Pietropaoli, Matthijn Vos, Giovanna Barba-Spaeth, Chiara Zurzolo. Tunneling nanotubes provide a novel route for SARS-CoV-2 spreading between permissive cells and to non-permissive neuronal cells. 2022. ⟨pasteur-03695860⟩

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