Inhibition of murine retrovirus-induced neurodegeneration in the spinal cord by explant culture.
AUTOR(ES)
Bessen, R A
RESUMO
The neurovirulent chimeric mouse ecotropic retrovirus FrCasE causes a rapid neurodegenerative disease of the central nervous system (CNS) characterized by the appearance of spongiform lesions in motor areas 10 days after neonatal inoculation. To study the details of the pathogenic process, we examined the ability of an ex vivo spinal cord model to recapitulate disease. Organotypic spinal cord slice cultures were established from IRW mice 7 days after neonatal inoculation. This corresponds to a time when virus expression in the CNS is first detectable but spongiform changes have yet to evolve. Infectivity associated with these cultures peaked at 7 days in vitro and persisted at this level for 6 weeks. FrCasE infection of the spinal cord slices was primarily found associated with microglial cells. Infection of neurons, astrocytes, 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 in organotypic cultures, no virus-specific spongiform degenerative changes were observed. These results suggest that removal of motor neurons from the developing CNS, despite maintaining the local cytoarchitectural relationships, prevents the virus from eliciting its pathological effects. Possible reasons for the interruption of lesion development are discussed.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=189658Documentos Relacionados
- Inhibition of retrovirus-induced disease in mice by camptothecin.
- Endoplasmic Reticulum Stress Is a Determinant of Retrovirus-Induced Spongiform Neurodegeneration
- Age-dependent resistance to murine retrovirus-induced spongiform neurodegeneration results from central nervous system-specific restriction of virus replication.
- Differential Glycosylation of the Cas-Br-E Env Protein Is Associated with Retrovirus-Induced Spongiform Neurodegeneration
- Murine retrovirus-induced depletion of T cells is mediated through activation-induced death by apoptosis.