Modelling cell infection in vitro can represent a useful tool to understand the susceptibility of different cell types towards SARS-CoV-2 and to decipher neurotropism. From this perspective, retinoic acid (RA)-differentiated neuroblastoma cell lines, SH-SY5Y and SK-N-BE(2) and glioblastoma cell lines, U-87 MG and U-373 MG, were infected with a SARS-CoV-2 strain, at various multiplicity-of-infection (MOI). The authors first demonstrated that the common entry genes – needed for invading epithelial cells – were expressed. RA-differentiation induced an upregulation of ACE2 and TMPRSS2 gene expression while inducing downregulation of CTSB and CTSL. Using in situ hybridisation and confocal analysis, SARS-CoV-2 gene S RNA was detected intracellularly at MOI 5.0, and localised in both soma and neuritic-like or glial-like processes. The infection was confirmed by quantification of viral gene E RNA and showed dose-dependency, with few infected cells at MOI 0.1. After 24 hours of infection, no cytopathic effect was observed in SH-SY5Y abilities to maintain neuritic processes or in U-373 MG for the uptake of glutamate. Unlike the permissive Vero E6 cells, no significant apoptosis death was detected following SARS-CoV-2 infection of neuroblastoma or glioblastoma cells. This study demonstrates the susceptibility of neuronal- and glial-like cell lines towards SARS-CoV-2 infection at high MOIs. Once inside the cells, the virus does not seem to rapidly replicate nor exert major cytopathic effects. Overall, these results strengthen the idea that SARS-CoV-2 demonstrates tropism for nervous cells that express commonly described entry genes.
DOI: 10.1016/j.brainres.2021.147344