To elucidate the early events in Theiler's virus-induced demyelination, a m
odel for human multiple sclerosis (MS), chemokine gene activation in the ce
ntral nervous system (CNS) resident cells upon viral infection was investig
ated. Viral infection selectively upregulated RANTES and IP-10 gene express
ion in primary astrocyte cultures and broader chemokine genes in oligodendr
ocyte and microglia cultures. Both RANTES and IP-10 were stimulated by proi
nflammatory cytokine interferon-gamma (IFN gamma), but only RANTES by tumor
necrosis factor alpha (TNF alpha), suggesting that virus infection induces
chemokines overlapping with those inducible by proinflammatory cytokines.
These results suggest that glial cells, astrocytes in particular, may be cr
itical for early recruitment or inflammatory cells in the initiation of vir
us-induced, immune-mediated demyelination. (C) 2001 Elsevier Science B.V. A
ll rights reserved.