[show abstract][hide abstract] ABSTRACT: We have determined whether Theiler's murine encephalomyelitis virus (TMEV), a picornavirus that produces demyelination in genetically susceptible strains of mice, induces c-fos in pure quiescent cultures of mouse brain astrocytes. As observed in Northern blots, the expression of this immediate early gene increases in a dose-dependent manner, with its expression peaking at a multiplicity of infection of 100. The expression of c-fos is transient, peaking after 30 min and disappearing 2 h after infection. The virus is quickly internalized at 37 degrees C upon binding to its specific receptor located at the cell surface and is actively replicated in the cytoplasm of the astrocytes, as demonstrated by FACS flow cytometry. Using the same technique, nuclear translation of c-fos mRNA is also shown. The specificity of viral induction is demonstrated by its neutralization with TMEV-specific antibodies and by the fact that only viral particles and not purified protein components VP1, VP2, and VP3 induced proto-oncogene expression. This rapid induction of c-fos in astrocytes could be the first stage in the infection of these central nervous system cell populations by TMEV. The biological relevance of these findings is assessed by the demonstration of c-fos activation after viral infection in vivo.