INHIBITION OF MURINE RETROVIRUS-INDUCED NEURODEGENERATION IN THE SPINAL-CORD BY EXPLANT CULTURE

The neurovirulent chimeric mouse ecotropic retrovirus FrCas(E) causes a rapid neurodegenerative disease of the central nervous system (CNS) characterized by the appearance of spongiform lesions in motor areas 1 0 days after neonatal inoculation. To study the details of the pathoge nic process, we examined the ability of an ex vivo spinal cord model t o recapitulate disease. Organotypic spinal cord slice cultures were es tablished from IRW mice 7 days after neonatal inoculation. This corres ponds to a time when virus expression in the CNS is first detectable b ut spongiform changes have yet to evolve. Infectivity associated with these cultures peaked at 7 days in vitro and persisted at this level f or 6 weeks, FrCas(E) infection of the spinal cord slices was primarily found associated with microglial cells. Infection of neurons, astrocy tes, oligodendroglia, and endothelial cells was not observed; however, significant astrogliosis was found. Despite the presence of extensive microglial infection in close association with spinal motor neurons i n organotypic cultures, no virus-specific spongiform degenerative chan ges were observed. These results suggest that removal of motor neurons from the developing CNS, despite maintaining the local cytoarchitectu ral relationships, prevents the virus from eliciting its pathological effects. Possible reasons for the interruption of lesion development a re discussed.