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Updated: Apr 16, 2026

A Model for Epilepsy of Infectious Etiology using Theiler's Murine Encephalomyelitis Virus
Published on: June 23, 2022
Lack of effect of Theiler's murine encephalomyelitis virus infection on system xc⁻
Ellen Merckx1, Thomas Demuyser2, Eduard Bentea1
1Department of Pharmaceutical Biotechnology and Molecular Biology, Center for Neurosciences (C4N), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
Abstract:
Changes in the expression of xCT, the specific subunit of system xc(-) or the cystine/glutamate antiporter, have been associated with several neurological disorders and system xc(-) was recently proposed as a potential target for the development of new treatment strategies for multiple sclerosis (MS). In this study we used Theiler's murine encephalomyelitis virus (TMEV) infection, both in vitro and in vivo, as a model to further evaluate the involvement of system xc(-) in MS. Protein levels of xCT, as well as activity of system xc(-) were unaffected in RAW264.7 macrophages after infection with the demyelinating DA strain of TMEV. Also, protein expression of xCT remained stable in spinal cord and brain of FVB mice 1-2 and 6 weeks after intracranial injection of the DA strain of TMEV. These results demonstrate that TMEV infection of macrophages or FVB mice has no effect on system xc(-) and as such cannot be used as a model to study the involvement of system xc(-) in MS.
Insights
The study found that Theiler's murine encephalomyelitis virus (TMEV) infection does not alter xCT expression or system xc(-) activity. Therefore, TMEV infection is not a suitable model for studying system xc(-) in multiple sclerosis (MS).
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- System xc(-) and its xCT subunit are implicated in neurological disorders.
- System xc(-) is a potential therapeutic target for multiple sclerosis (MS).
Purpose of the Study:
- To evaluate the involvement of system xc(-) in MS using Theiler's murine encephalomyelitis virus (TMEV) infection as a model.
- To assess changes in xCT expression and system xc(-) activity following TMEV infection in vitro and in vivo.
Main Methods:
- In vitro study of RAW264.7 macrophages infected with the DA strain of TMEV.
- In vivo study involving intracranial injection of the DA strain of TMEV into FVB mice.
- Analysis of xCT protein levels and system xc(-) activity.
Main Results:
- TMEV infection did not affect xCT protein levels or system xc(-) activity in macrophages.
- xCT protein expression remained stable in the spinal cord and brain of infected mice at 1-2 and 6 weeks post-infection.
- These findings indicate no modulation of system xc(-) by TMEV infection.
Conclusions:
- Theiler's murine encephalomyelitis virus (TMEV) infection does not impact system xc(-) function.
- TMEV infection in macrophages or FVB mice is not an appropriate model for investigating the role of system xc(-) in multiple sclerosis (MS).

