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

Autor: Charles Nicaise, Kevin Willemart, Florian Poulain, Nicolas Gillet, Noémie Avalosse, Riselane Lotfi, Jacques Gilloteaux, Noelle Ninanne, Noémie Lejeune, Kathleen De Swert, Valery Bielarz
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Cytoplasm
viruses
Cell
Neuroblastoma
0302 clinical medicine
RA
retinoic acid

tmprss2
transmembrane protease
serine 2

BBB
blood–brain barrier

Cytopathic effect
COVID-19
coronavirus disease 2019

ctsb
cathepsin B

General Neuroscience
Serine Endopeptidases
ish
in situ hybridization

medicine.anatomical_structure
Neurotropism
Angiotensin-Converting Enzyme 2
Cell type
SARS-CoV
severe acute respiratory syndrome coronavirus

Clinical Neurology
Biology
Models
Biological

Article
ctsl
cathepsin L

MOI
multiplicity-of-infection

03 medical and health sciences
Downregulation and upregulation
Cell Line
Tumor

medicine
Humans
Molecular Biology
Tropism
hprt
hypoxanthine–guanine phosphoribosyltransferase

SARS-CoV-2
ace2
angiotensin-converting enzyme 2

COVID-19
medicine.disease
Molecular biology
030104 developmental biology
Cell culture
Susceptibility
Vero cell
Neurology (clinical)
Glioblastoma
030217 neurology & neurosurgery
SARS-CoV-2
severe acute respiratory syndrome coronavirus-2

Developmental Biology
Zdroj: Brain Research
Bielarz, V, WILLEMART, KEVIN, Avalosse, N, De Swert, K, Lotfi, R, Lejeune, N, Poulain, F, Ninanne, N, GILLOTEAUX, J, GILLET, NICOLAS & Nicaise, C 2021, ' Susceptibility of neuroblastoma and glioblastoma cell lines to SARS-CoV-2 infection ', Brain research, vol. 1758, 147344 . https://doi.org/10.1016/j.brainres.2021.147344
ISSN: 1872-6240
DOI: 10.1016/j.brainres.2021.147344
Popis: 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.
Databáze: OpenAIRE