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[Theiler's virus encephalomyelitis infection as a model for multiple sclerosis: cytokines and pathogenic mechanisms]
E Molina-Holgado1, A Areválo-Martín, J M Vela
1Instituto Cajal. CSIC, Madrid, España.
Abstract:
Theiler's murine encephalomyelitis virus (TMEV) disease is induced following intracerebral inoculation of TMEV, a member of picornavirus family, in susceptible animals. The pathogenesis of paralytic syndrome is associated with a chronic progressive demyelinating disease characterized by perivascular of immune inflammatory cells. Although TMEV induced demyelinating disease (TMEV IDD) is initiated by virus specific CD4+ T cells targeting CNS persistent virus, CD4+ T cell responses against self myelin epitopes activated via epitope spreading contribute to chronic disease pathogenesis. In the present report we delineated possible pathogenic mechanisms related with inflammatory process, leading to demyelination and axonal loss. The importance of proinflammatory cytokines in sustaining the inflammatory process and cause direct oligodendrotoxicity is emphasized. Different approaches in therapeutic strategies affecting cytokines are also presented.
Insights
Theiler's murine encephalomyelitis virus (TMEV) infection causes a chronic demyelinating disease. Immune responses targeting viral and self-antigens, alongside inflammatory cytokines, drive disease progression and neuronal damage.
Area of Science:
- Neuroimmunology
- Virology
- Picornavirus research
Context:
- Theiler's murine encephalomyelitis virus (TMEV) infection in susceptible animals leads to a paralytic syndrome.
- This syndrome is characterized by chronic progressive demyelinating disease with perivascular immune cell infiltration in the central nervous system (CNS).
- TMEV-induced demyelinating disease (TMEV IDD) pathogenesis involves virus-specific CD4+ T cells and autoimmune responses to myelin epitopes via epitope spreading.
Purpose:
- To delineate pathogenic mechanisms underlying TMEV IDD, focusing on inflammation, demyelination, and axonal loss.
- To emphasize the role of proinflammatory cytokines in sustaining inflammation and causing direct oligodendrotoxicity.
- To present potential therapeutic strategies targeting cytokine modulation.
Summary:
- TMEV IDD pathogenesis is driven by both viral clearance mechanisms and autoimmune responses.
- Proinflammatory cytokines are crucial in perpetuating CNS inflammation and directly damaging oligodendrocytes, the myelin-producing cells.
- Epitope spreading, where immune responses broaden to self-antigens, contributes significantly to the chronic nature of the disease.
Impact:
- Understanding these mechanisms can inform the development of targeted therapies for TMEV IDD and potentially other demyelinating diseases.
- Highlighting the dual role of immune responses (viral and autoimmune) provides insights into managing chronic inflammatory CNS conditions.
- Identifying cytokine-dependent pathways offers therapeutic targets to mitigate neuroinflammation and preserve neuronal function.