Induction of selected chemokines in glial cells infected with Theiler's virus.

To elucidate the early events in Theiler's virus-induced demyelination, a model for human multiple sclerosis (MS), chemokine gene activation in the central nervous system (CNS) resident cells upon viral infection was investigated. Viral infection selectively upregulated RANTES and IP-10 gene expression in primary astrocyte cultures and broader chemokine genes in oligodendrocyte and microglia cultures. Both RANTES and IP-10 were stimulated by proinflammatory cytokine interferon-gamma (IFNgamma), but only RANTES by tumor necrosis factor alpha (TNFalpha), suggesting that virus infection induces chemokines overlapping with those inducible by proinflammatory cytokines. These results suggest that glial cells, astrocytes in particular, may be critical for early recruitment of inflammatory cells in the initiation of virus-induced, immune-mediated demyelination.