Viral Infection of Transgenic Mice Expressing a Viral Protein in Oligodendrocytes Leads to Chronic Central Nervous System Autoimmune Disease

Evans, Claire F.; Horwitz, Marc S.; Hobbs, Monte V.; Oldstone, Michael B.A.

This study describes a transgenic mouse model in which peripheral infection by a virus that shares immune epitopes with a protein expressed in oligodendrocytes led to CNS autoimmune disease. Without infecting the CNS, this virus induced disease characterized by chronic inflammation of the CNS and clinical motor dysfunction. This finding is significant, since several recent reports have provided evidence that molecular mimicry induced by a virus or other pathogen may play a role in the etiology of human CNS autoimmune diseases. For example, evidence for molecular mimicry between viral proteins and human MBP was found on the basis of structural similarities between an immunodominant MBP peptide and viral peptide sequences Figure 6 . Stimulation of increased CNS immune infiltration and activation of LCMV-memory CTL by infection with a second virus not encoding LCMV gene products. An MBP-NP transgenic positive mouse was infected with LCMV followed by VV infection 6 wk later. After another 6 wk, the mouse was sacrificed and increased numbers of CD8 Ï© (A) and CD4 Ï© (B) cells compared with those observed after a single LCMV infection were detected in the brain by immunohistochemical staining as described in Materials and Methods. Bar, 200 m; original magnification Ï«100.