Analysis of the leader and capsid coding regions of persistent and neurovirulent strains of Theiler's virus.

Most strains of Theiler's virus (TMEV) cause a persistent infection of the central nervous system of the mouse and a chronic demyelinating disease considered a model for multiple sclerosis. Two strains, on the contrary, cause an acute encephalitis and kill mice in a matter of days. We sequenced the leader and capsid coding region of three persistent (TO4, WW, and Yale) isolates and one neurovirulent (FA) isolate of TMEV. We compared these sequences and those already published for other isolates (DA, BeAn, GDVII, and Vilyuisk). The results suggest that virulent and persistent strains did not evolve as two separate groups, but rather that neurovirulent strains arose from a subgroup of persistent strains. The sequences of viruses isolated in different geographic areas and at different times were highly homologous, a surprising finding for an RNA virus. This suggests that severe constraints are imposed on the genome during the viral life cycle. The sequences of the TO4 and WW strains were identical, suggesting that the latter came from a laboratory contamination. The genomes of all the persistent strains sequenced so far contain an alternate open reading frame in the L region, which has been shown, in the case of the DA strain, to code for an 18-kDa protein called "I".