Theiler's murine encephalomyelitis virus preferentially infects immature stages of the murine oligodendrocyte precursor cell line BO-1 and blocks oligodendrocytic differentiation in vitro

Theiler's murine encephalomyelitis virus (TMEV)-induced demyelination is an important animal model for multiple sclerosis. The presence of oligodendrocyte precursor cells (OPCs) within demyelinated lesions together with the limited extent of remyelination has raised the question of how OPCs are affected by TMEV. It is well established that oligodendrocytes, astrocytes and microglia are targets during the chronic phase of the disease. However, whether TMEV infection interferes with the capacity of OPCs to generate oligodendrocytes has remained unclear. In the present study, a bipotential murine OPC cell line termed BO-1 was used to determine the antigenic phenotype susceptible to TMEV and the impact of TMEV infection upon cell differentiation. We show here that retinoic acid increased oligodendrocytic differentiation and decreased proliferation and TMEV infection rates. TMEV under serum-free conditions infected about 75% and 60% of early OPCs (NG(2+) and A2B5(+)) and immature oligodendrocytes (CNPase(+)), respectively, but only approximately 18% of mature oligodendrocytes (MBP+). Infection with TMEV prior to application of retinoic acid significantly reduced the percentage of MBP+ BO-1 cells. These data demonstrate that TMEV preferentially infects early stages of the oligodendrocytic lineage and blocks oligodendrocyte maturation. The first demonstration of TMEV-mediated effects on OPC differentiation may shed new light on the pathogenesis of TMEV-induced demyelination and offers an explanation for the limited remyelination observed in vivo. (C) 2010 Elsevier B.V. All rights reserved.