A PICORNAVIRAL PROTEIN SYNTHESIZED OUT OF FRAME WITH THE POLYPROTEIN PLAYS A KEY ROLE IN A VIRUS-INDUCED IMMUNE-MEDIATED DEMYELINATING DISEASE

The DA strain and other members of the TO subgroup of Theiler's murine encephalomyelitis virus (TMEV) induce a chronic demyelinating disease with a restricted virus expression. This disease serves as an experim ental model of multiple sclerosis; in both diseases the immune system contributes to a similar demyelinating pathology. Like all picornaviru ses, TMEV encodes a polyprotein translated from one long open reading frame. The polyprotein is then processed into structural and non-struc tural viral proteins. Here, we demonstrate that the DA strain of TMEV has an additional alternative open reading frame that encodes a protei n called L that is present in infected cells. Virus with a mutation o f L has a dramatically decreased demyelinating activity, indicating t hat L plays a critical role in TO subgroup-induced demyelinating dise ase. L is associated with membranes, suggesting that L* may interact with the immune system and thereby mediate the viral-induced demyelina ting disease.