SARS-CoV-2 tunnels to new cells【nature 2022年8月1日】

SARS-CoV-2 can cause neurological complications such as loss of smell or other central nervous system symptoms. It is unclear whether and to what extent the virus infects the brain, in particular as neuronal cells show low expression of ACE2, the cellular entry receptor of SARS-CoV-2. Pepe et al. find that SARS-CoV-2 can spread in vitro from Vero E6 cells, an epithelial cell line readily infected by SARS-CoV-2, to SH-SY5Y, a neuronal cell line, which is not permissive to the virus on its own. The authors show that tunnelling nanotubes (TNTs), thin membrane conduits, form between infected and uninfected cells and transport SARS-CoV-2 to the neuronal cells even though these receiving cells lack ACE2. This finding led the authors to suggest that spread through TNTs might contribute to central nervous system manifestations of COVID-19. It remains to be tested, however, whether TNTs also form and transport the virus in more physiologically relevant conditions and whether this form of spread indeed contributes to pathogenesis.

Tunneling nanotubes provide a route for SARS-CoV-2 spreading【Science 2022年7月20日】


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.