Analysis of the function of L^* protein of Theiler's virus (TV) by a lentiviral expression system

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DA subgroup strains of TV persist in the CNS of infected mice and induce demyelination. The mechanism(s) of virus persistence and demyelination remains unknown. DA subgroup strains synthesize a 17-kDa protein, called L^*, from an initiation site out-of-frame with the polyprotein. The previous study using a mutant virus, DAL^* 1 (in which the L^* AUG is substituted by an ACG), showed that L^* contributes to virus growth and has an anti-apoptotic effect in macrophages. Therefore, we established macrophage cell lines that continuatively express L^*, in order to confirm its role in TV growth and apoptosis, which may be important in TMEV pathogenesis. A "gain of function" experiment using L^*-expressing macrophages demonstrated that L^* protein of TMEV is essential for virus growth and has an anti-apoptotic effect in those macrophage cell lines.