Neurodegeneration induced by MoMuLV-ts1 and increased expression of Fas and TNF-alpha in the central nervous system.

Infection of neonatal mice with ts1, the neuropathogenic mutant of the Moloney murine leukemia virus, results in motor neuronal death in the brainstem and the spinal cord, with gliosis and demyelination, but no inflammatory cell infiltration into the CNS. To evaluate the possible mechanism(s) of ts1-induced neuropathogenesis, we measured CNS expression of cytokines and cell death-related genes in ts1-infected mice with neurological signs and compared with control uninfected mice. In the brainstem, the expression of Fas and tumor necrosis factor alpha (TNF-alpha) was increased in the ts1-infected mice. Both TNF-alpha and Fas were detected in astrocytes, and Fas was also detected in neurons in the brainstem. Some TNF-alpha-immunolabeled cells also appeared to be microglial cells. Most Fas-positive cells, including astrocytes and neurons, showed cytoplasmic vacuolization and other degenerative changes. In addition, Fas ligand-immunolabeled cells were also detected in sites where spongiform degeneration occurred. This study suggests that neural cell death in ts1-induced neurodegeneration is likely due to Fas- and TNF-alpha-mediated cell death mechanisms.