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Updated: Feb 28, 2026
A Model for Epilepsy of Infectious Etiology using Theiler's Murine Encephalomyelitis Virus
Published on: June 23, 2022
Three immune-mediated disease models induced by Theiler's virus: Multiple sclerosis, seizures and myocarditis
Ikuo Tsunoda1, Fumitaka Sato1, Seiichi Omura1
1Department of Microbiology, Kindai University Faculty of Medicine, Osakasayama, Osaka, Japan.
Abstract:
Theiler's murine encephalomyelitis virus (TMEV) infection has been used as a viral model for multiple sclerosis (MS), as TMEV can induce chronic inflammatory demyelinating lesions with viral persistence in the spinal cord of SJL/J mice. In contrast, when C57BL/6 mice are infected with TMEV, the mice can clear the virus from the central nervous system (CNS), without viral persistence or demyelination, but develop seizures and hippocampal sclerosis, which has been used as a viral model for seizures/epilepsy. In the two TMEV-induced CNS disease models, not only viral infection, but also immune responses contribute to the pathogenesis. Interestingly, acquired immunity plays an effector role in the MS model, whereas innate immunity appears to contribute to the development of seizures. Recently, we have established the third TMEV-induced disease model, a mouse model for viral myocarditis, using C3H mice. TMEV-induced myocarditis is a triphasic disease, which mimics human myocarditis; phase I, mediated by viral replication in the heart and innate immunity; phase II, mediated by acquired immunity; and phase III, resulted from cardiac fibrosis. The genetic susceptibility to the aforementioned three models (MS, seizures and myocarditis) differs among mouse strains. We have compared and contrasted the three models induced by one single pathogen, TMEV, particularly in regard to the roles of T helper cells and natural killer T cells, which will give an insight into how interactions between the immune system and the host's genetic background determine the tissue tropism of virus and the development of virus-induced organ-specific immunopathology.
Insights
Theiler
Area of Science:
- Virology
- Immunology
- Neuroscience
- Cardiology
Background:
- Theiler's murine encephalomyelitis virus (TMEV) infection serves as a valuable tool for studying viral-induced diseases.
- TMEV infection in mice can lead to distinct organ-specific pathologies, including demyelinating lesions (multiple sclerosis model), seizures (epilepsy model), and viral myocarditis.
- Genetic background of the host mouse strain significantly influences disease outcome and susceptibility to TMEV infection.
Purpose of the Study:
- To compare and contrast three distinct TMEV-induced disease models in mice: multiple sclerosis, seizures, and viral myocarditis.
- To investigate the roles of innate and acquired immunity, specifically T helper cells and natural killer T cells, in the pathogenesis of these TMEV-induced diseases.
- To elucidate how host genetic factors interact with viral infection and immune responses to determine tissue tropism and organ-specific immunopathology.
Main Methods:
- Infection of different mouse strains (SJL/J, C57BL/6, C3H) with Theiler's murine encephalomyelitis virus (TMEV).
- Analysis of viral persistence, demyelination, hippocampal sclerosis, and cardiac pathology.
- Assessment of immune responses, including the roles of T helper cells and natural killer T cells, in disease development.
Main Results:
- TMEV infection in SJL/J mice induces chronic inflammatory demyelinating lesions, modeling multiple sclerosis.
- TMEV infection in C57BL/6 mice leads to viral clearance but results in seizures and hippocampal sclerosis, modeling epilepsy.
- TMEV infection in C3H mice establishes a triphasic model of viral myocarditis, involving viral replication, acquired immunity, and cardiac fibrosis.
Conclusions:
- The study highlights the distinct immunopathogenesis of TMEV-induced diseases, influenced by host genetics and immune responses.
- Innate immunity is crucial for seizure development, while acquired immunity plays a role in multiple sclerosis pathogenesis.
- Understanding these TMEV models provides insights into virus-host interactions and the development of organ-specific inflammatory diseases.
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