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Neuropathogenesis of Theiler’s Murine Encephalomyelitis Virus Infection, An Animal Model for Multiple Sclerosis

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Abstract

Theiler’s murine encephalomyelitis virus (TMEV) infection of mice is an experimental model for multiple sclerosis (MS). TMEV induces a biphasic disease in susceptible mouse strains. During the acute phase, 1 week after infection, TMEV causes polioencephalomyelitis characterized by infection and apoptosis of neurons in the gray matter of the brain. During the chronic phase, about 1 month after infection, virus infects glial cells and macrophages, and induces inflammatory demyelination with oligodendrocyte apoptosis and axonal degeneration in the white matter of the spinal cord. Although antibody, CD4+, and CD8+ T cell responses against TMEV capsid proteins play important roles in neuropathogenesis, infectious virus with persistence is necessary to induce demyelination; in general, adoptive transfer of antibody or T cells alone did not induce central nervous system (CNS) disease. The TMEV model can be useful for testing new therapeutic strategies specifically as a viral model for MS. Therapies targeting adhesion molecules, axonal degeneration, and immunosuppression can be beneficial for pure autoimmune CNS demyelinating diseases, such as experimental autoimmune encephalomyelitis, but could be detrimental in virus-induced demyelinating diseases, such as progressive multifocal leukoencephalopathy.

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Acknowledgements

We thank Nikki J. Kirkman BS and Jane E. Libbey MS for many helpful discussions, and Daniel Doty, Faris Hasanovic BS, Krystal D. Porter BS, and Reina Yamaji MD for excellent technical assistance. We are grateful to Ms. Kathleen Borick for preparation of the manuscript.

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  1. Ikuo Tsunoda

    Present address: Department of Microbiology and Immunology, Louisiana State University Health Science Center, 1501 Kings Highway, Shreveport, LA, 71130, USA

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  1. Department of Pathology, University of Utah School of Medicine, 30 North 1900 East, 3R330 SOM, Salt Lake City, UT, 84132, USA

    Ikuo Tsunoda & Robert S. Fujinami

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  1. Ikuo Tsunoda
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  2. Robert S. Fujinami
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Correspondence to Robert S. Fujinami.

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This work was supported by NIH grants 1R21NS059724 (IT) and 1P01AI058105 (RSF).

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Tsunoda, I., Fujinami, R.S. Neuropathogenesis of Theiler’s Murine Encephalomyelitis Virus Infection, An Animal Model for Multiple Sclerosis. J Neuroimmune Pharmacol 5, 355–369 (2010). https://doi.org/10.1007/s11481-009-9179-x

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