Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo Tokyo, Japan.
Front Microbiol. 2011 Aug 23;2:173. doi: 10.3389/fmicb.2011.00173. eCollection 2011.
Measles, caused by measles virus (MeV) infection, is the leading cause of death in children because of secondary infections attributable to MeV-induced immune suppression. Recently, we have shown that wild-type MeVs induce the suppression of protein synthesis in host cells (referred to as "shutoff") and that viral mRNAs are preferentially translated under shutoff conditions in infected cells. To determine the mechanism behind the preferential translation of viral mRNA, we focused on the 5' untranslated region (UTR) of nucleocapsid (N) mRNA. The La/SSB autoantigen (La) was found to specifically bind to an N-5'UTR probe. Recombinant La enhanced the translation of luciferase mRNA containing the N-5'UTR (N-fLuc), and RNA interference of La suppressed N-fLuc translation. Furthermore, recombinant MeV lacking the La-binding motif in the N-5'UTR displayed delayed viral protein synthesis and growth kinetics at an early phase of infection. These results suggest that La induced predominant translation of N mRNA via binding to its 5'UTR under shutoff conditions. This is the first report on a cellular factor that specifically regulates paramyxovirus mRNA translation.
麻疹是由麻疹病毒（MeV）感染引起的，是导致儿童死亡的主要原因，因为 MeV 引起的免疫抑制会导致继发感染。最近，我们已经表明，野生型 MeVs 会诱导宿主细胞中的蛋白质合成抑制（称为“关闭”），并且在感染细胞中，病毒 mRNA 在关闭条件下优先翻译。为了确定病毒 mRNA 优先翻译的机制，我们专注于核衣壳（N）mRNA 的 5'非翻译区（UTR）。发现 La/SSB 自身抗原（La）特异性结合 N-5'UTR 探针。重组 La 增强了含有 N-5'UTR 的荧光素酶 mRNA（N-fLuc）的翻译，而 La 的 RNA 干扰抑制了 N-fLuc 翻译。此外，重组 MeV 缺失 N-5'UTR 中的 La 结合基序，在感染早期表现出病毒蛋白合成和生长动力学的延迟。这些结果表明，La 在关闭条件下通过结合其 5'UTR 诱导 N mRNA 的优先翻译。这是第一个关于特定调节副粘病毒 mRNA 翻译的细胞因子的报告。
