Isolation and characterization of two plaque size variants of Theiler's murine encephalomyelitis virus (DA strain)

We have isolated two plaque size variants of Theiler's murine encephalomyelitis virus (TMEV) strain DA. One variant, TMEV-CL (CL), produced large plaques, while the other, TMEV-DS (DS), produced small plaques in L-2 cells. The DS variant yielded a lower titre in BHK cells and had a significantly slower growth rate when compared to CL and DA. In contrast, DS replicated to a higher titre in the central nervous system (CNS) of infected mice than the large plaque counterpart and DA. Furthermore, the DS (but not CL) variant was temperature-sensitive, replicating 130- to 500-fold more at 37 degrees C than at 39 degrees C. Although DS, CL and DA were able to establish persistent CNS infections in mice, only the DS variant and DA induced demyelinating disease in SJL/J mice. Therefore persistence of TMEV in the CNS is not sufficient to produce demyelinating disease. These two variants of the DA strain of TMEV will be useful for study of the viral genetic elements important in the mechanism of virus-induced demyelination.