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.
Pepe, A. et al. Tunneling nanotubes provide a route for SARS-CoV-2 spreading. Sci. Adv. https://doi.org/10.1126/sciadv.abo0171 (2022)
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Hofer, U. SARS-CoV-2 tunnels to new cells. Nat Rev Microbiol 20, 576 (2022). https://doi.org/10.1038/s41579-022-00788-9