The immune response to TMEV involves activation of both the innate and adaptive immune responses. The innate immune response is the initial response by the host to a viral infection. The adaptive immune response follows the initial response and is mediated by CD8+ and CD4+ T cell and antibody responses specific to the viral antigens. CNS pathogenesis in TMEV-IDD is associated with long-term virus persistence in CNS-resident microglia and macrophages which leads to the activation of a virus-specific CD4+ Th1 response. Myelin destruction is initiated by the bystander effector functions of CNS-resident mononuclear cells which are activated both directly by the innate immune response to persistent TMEV infection and indirectly by pro-inflammatory cytokines released by virus-specific Th1 cells. Initial myelin destruction leads to the release of myelin antigens and the subsequent activation of myelin epitope-specific autoreactive CD4+ Th1 cells via epitope spreading which are largely responsible for chronic disease progression.
- Theiler's murine encephalomyelitis virus (TMEV)
- demyelinating disease
- epitope spreading
- molecular mimicry
- multiple sclerosis