THEILERS MURINE ENCEPHALOMYELITIS VIRUS KILLS RESTRICTIVE BUT NOT PERMISSIVE CELLS BY APOPTOSIS

Theiler's murine encephalomgelitis viruses (TMEV), genus Cardiovirus, family Piconiviridae, are natural enteric pathogens of mice which caus e central nervous system demyelination similar to that seen in multipl e sclerosis, TMEV can be classified into mo groups based on neurovirul ence: a highly virulent group, e.g., GDVII virus, and a less virulent group, e.g., BeAn virus. Both viruses, depending on the multiplicity o f infection, produced cytopathology in BSC-1 cells similar to that in BHK-21 cells, Since apoptosis has been reported as a mechanism of cell death after infection with many viruses, we examined infected BHK-21 and BSC-1 cells for morphological and biochemical changes consistent w ith apoptosis, Only the restrictive BSC-1 cells showed evidence of nuc lear morphology and internucleosomal DNA degradation indicative of apo ptosis, Interestingly, the more virulent GDVII virus was at least 50-f old more efficient in inducing apoptosis than the less virulent BeAn v irus, This difference was not due to greater GDVII viral RNA replicati on or production of infectious virus, since the two viruses were simil arly restricted in BSC-I cells, Apoptosis in BSC-1 cells appears to be triggered by a cytoplasmic event, since inactivation of GDVII viral R NA by UV light abolished the ability of the virus to induce apoptosis, The possible role of apoptosis in the pathogenesis of TMEV infection in mice, especially virus persistence in central nervous system macrop hages, is discussed.