Journal of Neuroimmune Pharmacology

, Volume 5, Issue 3, pp 355–369 | Cite as

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

  • Ikuo Tsunoda
  • Robert S. FujinamiEmail author
Invited Review


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.


adhesion molecules apoptosis axonal damage central nervous system experimental autoimmune encephalomyelitis inside–out model 



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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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of PathologyUniversity of Utah School of MedicineSalt Lake CityUSA
  2. 2.Department of Microbiology and ImmunologyLouisiana State University Health Science CenterShreveportUSA

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