Norovirus-Mediated Modification of the Translational Landscape via Virus and Host-Induced Cleavage of Translation Initiation Factors.
Norovirus-Mediated Modification of the Translational Landscape via Virus and Host-Induced Cleavage of Translation Initiation Factors.
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DOI：
10.1074/mcp.m116.062448
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发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Goodfellow I
中科院分区：
文献类型：
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作者：
Emmott E;Sorgeloos F;Caddy SL;Vashist S;Sosnovtsev S;Lloyd R;Heesom K;Locker N;Goodfellow I
诺如病毒产生缺乏 5' 帽结构的病毒 RNA，而是使用病毒编码的病毒蛋白基因组连锁 (VPg) 蛋白与病毒 RNA 共价连接，与翻译起始因子相互作用并驱动病毒蛋白合成。诺如病毒感染会诱导先天反应，导致干扰素刺激基因 (ISG) 转录。然而，诱导的 ISG mRNA 的翻译受到抑制。采用基于 SILAC 的质谱方法分析全细胞和富含 m7GTP 的样品中蛋白质丰度的变化，以证明宿主 mRNA 翻译的减少与真核起始因子复合物的组成变化相关。宿主 ISG 翻译的抑制与病毒蛋白酶 (NS6) 的活性和导致细胞凋亡环境建立的细胞半胱天冬酶的激活相关。这些结果表明，诺如病毒利用病毒 VPg 依赖性翻译和细胞帽依赖性翻译之间的差异来减弱宿主对感染的反应。
Noroviruses produce viral RNAs lacking a 5′ cap structure and instead use a virus-encoded viral protein genome-linked (VPg) protein covalently linked to viral RNA to interact with translation initiation factors and drive viral protein synthesis. Norovirus infection results in the induction of the innate response leading to interferon stimulated gene (ISG) transcription. However, the translation of the induced ISG mRNAs is suppressed. A SILAC-based mass spectrometry approach was employed to analyze changes to protein abundance in both whole cell and m7GTP-enriched samples to demonstrate that diminished host mRNA translation correlates with changes to the composition of the eukaryotic initiation factor complex. The suppression of host ISG translation correlates with the activity of the viral protease (NS6) and the activation of cellular caspases leading to the establishment of an apoptotic environment. These results indicate that noroviruses exploit the differences between viral VPg-dependent and cellular cap-dependent translation in order to diminish the host response to infection.