Susceptibility of neuroblastoma and glioblastoma cell lines to SARS-CoV-2 infection

Valery Bielarz, KEVIN WILLEMART, Noémie Avalosse, Kathleen De Swert, Riselane Lotfi, Noemie Lejeune, Florian Poulain, Noelle Ninanne, Jacques GILLOTEAUX, NICOLAS GILLET, Charles Nicaise

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Abstract

Modelling cell infection in-a-dish can represent a useful tool to understand the susceptibility of different cell types towards severe acute respiratory coronavirus-2 (SARS-CoV-2) and to decipher its neurotropism. In 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). We 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 hybridization and confocal analysis, SARS-CoV-2 gene S RNA was detected intracellularly at MOI 5.0, and localized in both soma and neuritic-like or glial-like processes. The infection was confirmed by quantification of viral gene E RNA and showed a dose-dependency, with few infected cells at MOI 0.1. After 24 h 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 effect. Overall, our results strengthen the idea that SARS-CoV-2 has a tropism for nervous cells that express commonly described entry genes.

Original languageEnglish
Article number147344
JournalBrain research
Volume1758
DOIs
Publication statusPublished - 5 Feb 2021

Keywords

  • SARS-CoV-2
  • neuroblastoma
  • Glioblastoma
  • neurotropism
  • cytopathic effect
  • susceptibility
  • Susceptibility
  • Cytopathic effect
  • Neurotropism
  • Neuroblastoma

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