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

Anna Pepe (1) , Stefano Pietropaoli (2, 3) , Matthijn Vos (4) , Giovanna Barba-Spaeth (2) , Chiara Zurzolo (1)

1 Trafic membranaire et Pathogénèse - Membrane Traffic and Pathogenesis
2 Virologie Structurale - Structural Virology
3 Catalent Phama Solution
4 Plateforme technologique Nanoimagerie / Nanoimaging Technological Platform

Neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection represent a major issue in long coronavirus disease. How SARS-CoV-2 gains access to the brain and how infection leads to neurological symptoms are not clear because the principal means of viral entry by endocytosis, the angiotensin-converting enzyme 2 receptor, are barely detectable in the brain. We report that human neuronal cells, nonpermissive to infection through the endocytic pathway, can be infected when cocultured with permissive infected epithelial cells. SARS-CoV-2 induces the formation of tunneling nanotubes (TNTs) and exploits this route to spread to uninfected cells. In cellulo correlative fluorescence and cryo–electron tomography reveal that SARS-CoV-2 is associated with TNTs between permissive cells. Furthermore, multiple vesicular structures such as double-membrane vesicles, sites of viral replication, are observed inside TNTs between permissive and nonpermissive cells. Our data highlight a previously unknown mechanism of SARS-CoV-2 spreading, likely used as a route to invade nonpermissive cells and potentiate infection in permissive cells

Domaines: Biochimie, Biologie Moléculaire

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. Science Advances , 2022, 28 (9), ⟨10.1101/2021.11.15.468633⟩. ⟨pasteur-03695860v2⟩