Chung Liliane, Bailey Dalan, Leen Eoin N, Emmott Edward P, Chaudhry Yasmin, Roberts Lisa O, Curry Stephen, Locker Nicolas, Goodfellow Ian G
From the Section of Virology, Department of Medicine, Imperial College London, Norfolk Place, London W2 1PG, United Kingdom.
From the Section of Virology, Department of Medicine, Imperial College London, Norfolk Place, London W2 1PG, United Kingdom, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
J Biol Chem. 2014 Aug 1;289(31):21738-50. doi: 10.1074/jbc.M114.550657. Epub 2014 Jun 13.
Viruses have evolved a variety of mechanisms to usurp the host cell translation machinery to enable translation of the viral genome in the presence of high levels of cellular mRNAs. Noroviruses, a major cause of gastroenteritis in man, have evolved a mechanism that relies on the interaction of translation initiation factors with the virus-encoded VPg protein covalently linked to the 5' end of the viral RNA. To further characterize this novel mechanism of translation initiation, we have used proteomics to identify the components of the norovirus translation initiation factor complex. This approach revealed that VPg binds directly to the eIF4F complex, with a high affinity interaction occurring between VPg and eIF4G. Mutational analyses indicated that the C-terminal region of VPg is important for the VPg-eIF4G interaction; viruses with mutations that alter or disrupt this interaction are debilitated or non-viable. Our results shed new light on the unusual mechanisms of protein-directed translation initiation.
病毒已经进化出多种机制来篡夺宿主细胞的翻译机器，以便在存在高水平细胞mRNA的情况下实现病毒基因组的翻译。诺如病毒是人类肠胃炎的主要病因，它进化出了一种机制，该机制依赖于翻译起始因子与共价连接到病毒RNA 5' 末端的病毒编码VPg蛋白之间的相互作用。为了进一步表征这种新型的翻译起始机制，我们利用蛋白质组学来鉴定诺如病毒翻译起始因子复合物的组成成分。这种方法揭示了VPg直接与eIF4F复合物结合，VPg与eIF4G之间发生高亲和力相互作用。突变分析表明，VPg的C末端区域对于VPg-eIF4G相互作用很重要；具有改变或破坏这种相互作用的突变的病毒会减弱或无法存活。我们的结果为蛋白质定向翻译起始的异常机制提供了新的线索。
