Theiler's murine encephalomyelitis virus infection induces early expression of c-fos in astrocytes

We have determined whether Theiler's murine encephalomyelitis virus (TMEV), a picornavirus that produces demyelination in genetically susceptible stra ins of mice, induces c-fos in pure quiescent cultures of mouse brain astroc ytes. 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, p eaking after 30 min and disappearing 2 h after infection. The virus is quic kly internalized at 37 degrees C upon binding to its specific receptor loca ted at the cell surface and is actively replicated in the cytoplasm of the astrocytes, as demonstrated by FAGS flow cytometry. Using the same techniqu e, nuclear translation of c-fos mRNA is also shown. The specificity of vira l induction is demonstrated by its neutralization with TMEV-specific antibo dies and by the fact that only viral particles and not purified protein com ponents VP1, VP2, and VP3 induced proto-oncogene expression. This rapid ind uction of c-fos in astrocytes could be the first stage in the infection of these central nervous system cell populations by TMEV. The biological relev ance of these findings is assessed by the demonstration of c-fos activation after viral infection in vivo. (C) 1999 Academic Press.