Raymond Roos MD is investigating Theiler’s virus (TV), a mouse picornavirus that produces interesting neurological disease phenotypes. Certain strains from one TV subgroup produce a chronic persistent infection in mice in which autoimmune factors mediate a demyelinating disease. The demyelination caused by these strains provides one of the best experimental models for MS because of the similarity in their pathology and because the immune system appears to contribute to disease in both cases. Other strains from a second TV subgroup cause a motor neuron disease. The Roos lab is investigating Theiler's virus (TV)-induced disease in order to identify molecular determinants for demyelination and neurovirulence and the mechanisms involved. The basic aim is to define molecular determinants for the virus' biological behavior. The TV model is an especially valuable one for these studies because of the powerful molecular tools that are available, the interesting phenotypes of the strains, and the ease with which one can study this simple virus in a mouse (including various mouse mutant strains). With this goal in mind, the Roos lab has produced infectious cDNA clones from strains of the two different subgroups and generated recombinant and mutated viruses. The identification of the virus genes may not only clarify the pathogenesis of TV disease, but also lead to an understanding of genes important in the normal CNS and in human CNS disease states (such as MS and motor neuron disease).