Theiler's murine encephalomyelitis virus (TMEV) strains are divided into two subgroups on the basis of their differing disease phenotypes. Members of the GDVII subgroup, such as GDVII strain, produce an acute lethal polioencephalomyelitis. In contrast, members of the TO subgroup, such as DA strain, induce a persistent infection with chronic demyelination; this white matter disease serves as an experimental model of multiple sclerosis (MS) due to their similar pathology and because the immune system in both diseases appears to contribute to the demyelination. The availability of full-length infectious TMEV clones, the relative simplicity of the TMEV genome, and the availability of the mouse as a host provide the opportunity to identify molecular determinants and disease mechanisms that are responsible for neurovirulence, demyelination and virus persistence, and makes this a valuable system for pathogenesis studies.