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中枢神经系统中持续存在并诱导脱髓鞘。病毒持续存在和脱髓鞘的机制尚不清楚。DA亚群菌株从与多蛋白框外的起始位点合成一个17 kda的蛋白，称为L^*。先前使用突变病毒DAL^* 1（其中L^* AUG被ACG取代）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，这可能在TMEV发病机制中起重要作用。用L^*表达的巨噬细胞进行的“功能增益”实验表明，TMEV的L^*蛋白对病毒生长至关重要，并在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.