TMEV and neuroantigens: Myelin genes and proteins, molecular mimicry, epitope spreading, and autoantibody-mediated remyelination

Abstract

The Theiler's murine encephalomyelitis (TMEV) model has been used to study the interactions of virus, myelin and anti-neuroantigen autoimmunity, TMEV and myelin can interrelate during virus entry and persistence. On virus entry, TMEV might use peripheral myelin P0 protein as a virus receptor. For persistence, TMEV seems to require myelin functional proteins or structural myelin itself. Here, myelin and oligodendrocyte loss and downregulation of myelin genes would lead to demyelination, but might limit virus spread in the central nervous system. Unlike experimental allergic encephalomyelitis (EAE), a pathogenic role of anti-myelin autoimmunity is unclear in TMEV infection. Anti-myelin autoantibodies have been detected in TMEV infection. Among them, only anti-galactocerebroside (GC) antibody is shown to be myelinotoxic, and has molecular mimicry with TMEV. Myelin-specific T cells play no role in initiation or progression of demyelination in the first two to three months after TMEV infection. However, cellular autoimmunity against several myelin antigens (epitope spreading) can be detected during the late chronic stage. Using the TMEV model, epitope spreading and autoantibody-mediated remyelination have been investigated by recombinant TMEV and anti-neuroantigen (natural) antibodies, respectively