Molecular pathogenesis of Theiler's murine encephalomyelitis virus-induced demyelinating disease in mice.

After an acute phase of virus growth in neurons (e.g. anterior horn cells), Theiler's murine encephalomyelitis virus (TMEV) persists as a chronic productive infection, largely in macrophages in the CNS white matter. TMEV replication in macrophages is highly restricted, probably as the result of host cell factors. The preponderance of evidence indicates that TMEV persistence leads to immunopathologic damage of myelin, mediated by major histocompatibility class II-restricted Th1 lymphocytes directed at a virus epitope(s) rather than host neuroantigens at least early in the infection. Analysis of TMEV recombinant and mutant viruses suggests that persistence requires a specific capsid conformation involving the VP2 puff and VP1 loops, which may influence persistence through virion receptor binding or attachment to host cells, e.g. macrophages.