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Growth and neurovirulence of a number of neurotropic viruses show pronounced differences after passage in cell culture compared with continued in vivo passage in the central nervous system. The DA strain of Theiler's murine encephalomyelitis virus provides a model for studying these issues since DA virus grown in mouse brain produces acute neuronal disease in weanling mice, but tissue culture-passed DA virus does not. In addition, DA virus grown in mouse brain has a greater 50% mouse lethal dose/50% tissue culture infective dose ratio than tissue culture-passed DA virus. Comparison of these viruses required the analysis of virus purified directly from infected mouse brain, without tissue culture passage. Capsid proteins from DA virus grown in mouse brain were resolved on sodium dodecyl sulfate-polyacrylamide gels and shown to have the same profile as tissue culture-passed DA virus. Viral RNAs were the same size, with no evidence of defective interfering particle production. Two-dimensional gels of in vitro-labeled RNase T1-digested RNA showed that virus variants were more apparent during acute in vivo passage. These genomic differences may be critical in determining the biological behavior of the virus.

Biochemical analysis of DA strain of Theiler's murine encephalomyelitis virus obtained directly from acutely infected mouse brain