VIRAL-INFECTION OF TRANSGENIC MICE EXPRESSING A VIRAL PROTEIN IN OLIGODENDROCYTES LEADS TO CHRONIC CENTRAL-NERVOUS-SYSTEM AUTOIMMUNE-DISEASE

One hypothesis for the etiology of central nervous system (CNS) autoim mune disease is that infection by a virus sharing antigenic epitopes w ith CNS antigens (molecular mimicry) elicits a virus-specific immune r esponse that also recognizes self-epitopes. To address this hypothesis , transgenic mice were generated that express the nucleoprotein or gly coprotein of lymphocytic choriomeningitis virus (LCMV) as self in olig odendrocytes. Intraperitoneal infection with LCMV strain Armstrong led to infection of tissues in the periphery but not the CNS, and the vir us was cleared within 7-14 d. After clearance, a chronic inflammation of the CNS resulted, accompanied by upregulation of CNS expression of MHC class I and II molecules. A second LCMV infection led to enhanced CNS pathology, characterized by loss of myelin and clinical motor dysf unction. Disease enhancement also occurred after a second infection wi th unrelated viruses that cross-activated LCMV-specific memory T cells . These findings indicate that chronic CNS autoimmune disease may be i nduced by infection with a virus sharing epitopes with a protein expre ssed in oligodendrocytes and this disease may be enhanced by a second infection with the same or an unrelated virus. These results may expla in the association of several different viruses with some human autoim mune diseases.