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

TV的DA亚群菌株在感染小鼠的CNS中持续存在并诱导脱髓鞘。病毒持续存在和脱髓鞘的机制仍不清楚。DA亚群菌株从多聚蛋白的框架外起始位点合成一种17 kDa的蛋白质，称为L^*。先前使用突变病毒DAL^* 1（其中L^* AUG被ACG取代）进行的研究表明，L^* 有助于病毒生长，并在巨噬细胞中具有抗凋亡作用。因此，我们建立了持续表达L^* 的巨噬细胞系，以证实其在TV生长和凋亡中的作用，这在TMEV发病机制中可能是重要的。使用表达L^* 的巨噬细胞进行的“功能获得”实验表明，TMEV的L^* 蛋白对于病毒生长是必需的，并且在这些巨噬细胞系中具有抗凋亡作用。

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.