Apoptosis in acute and chronic central nervous system disease induced by Theiler's murine encephalomyelitis virus

Apoptosis has been observed in neural development and in various neurological diseases, including viral infection and multiple sclerosis. Theiler's murine encephalomyelitis virus is divided into two subgroups based on neurovirulence: the highly neurovirulent GDVII strain produces an acute fatal polioencephalomyelitis in mice, whereas the attenuated DA strain produces demyelination with virus persistence preceded by an acute infection. TUNEL combined with immunocytochemistry was used to detect apoptosis in the central nervous system and to characterize which cell types were involved during the acute stage in both GDVII and DA virus infection and during the chronic stage in DA virus infection. We found that during the acute stage, apoptosis was induced in neurons in both virus infections. However, the number of apoptotic neurons was much greater in GDVII virus-infected mice than in DA virus-infected mice (P < 0.01). During the chronic stage of DA virus infection, apoptotic cells were detected only in the spinal cord white matter. Some of these cells were dual labeled for fragmented DNA and carbonic anhydrase II, an oligodendrocyte marker. Our results indicate that apoptosis of neurons could be responsible for the fatal outcome in GDVII virus infection. In contrast, apoptosis of oligodendrocytes can contribute to the chronic demyelinating DA virus infection.