Murine norovirus 1 (MNV1) replication induces translational control of the host by regulating eIF4E activity during infection.
Murine norovirus 1 (MNV1) replication induces translational control of the host by regulating eIF4E activity during infection.
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DOI：
10.1074/jbc.m114.602649
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发表时间：
2015-02-20
期刊：
影响因子：
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通讯作者：
Locker N
中科院分区：
文献类型：
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作者：
Royall E;Doyle N;Abdul-Wahab A;Emmott E;Morley SJ;Goodfellow I;Roberts LO;Locker N
背景：eIF4E的磷酸化在控制蛋白质翻译中起着关键作用。结果：MNV1感染可导致p-eIF4E的激活、向多聚体迁移和翻译调控。结论：MNV1通过控制eIF4E活性来操纵宿主细胞的翻译机制。意义：细胞对感染反应的调节可能有助于病毒的发病和持续。蛋白质合成是一个严格控制的过程，对几种刺激做出反应，包括病毒感染。作为专性的细胞内寄生虫，病毒依赖于宿主的翻译机制，并可以通过影响特定的真核细胞起始因子(EIF)的可用性和功能来操纵它。人类诺如病毒是杯状病毒科的成员，是胃肠炎爆发的罪魁祸首。以往对猫杯状病毒和小鼠诺如病毒1(MNV1)的研究表明，病毒蛋白基因组连锁(VPG)通过劫持宿主蛋白质合成机制来指导翻译。在此，我们报道了MNV1感染调节MAPK通路激活eIF4E磷酸化。我们的结果表明，在MNV1感染过程中p38和MNK的激活对MNV1的复制是重要的。此外，磷酸化的eIF4E重新定位到多聚体，这有助于特定宿主mRNAs翻译状态的改变。我们认为，eIF4E磷酸化对宿主的整体翻译控制是宿主与病原体相互作用的关键组成部分。
Background: The phosphorylation of eIF4E plays a critical role in controlling protein translation. Results: MNV1 infection results in activation of p-eIF4E, its relocation to polysomes, and translational regulation. Conclusion: MNV1 manipulates the host cell translation machinery by controlling eIF4E activity. Significance: Regulation of cellular response to infection may contribute to viral pathogenesis and persistence. Protein synthesis is a tightly controlled process responding to several stimuli, including viral infection. As obligate intracellular parasites, viruses depend on the translation machinery of the host and can manipulate it by affecting the availability and function of specific eukaryotic initiation factors (eIFs). Human norovirus is a member of the Caliciviridae family and is responsible for gastroenteritis outbreaks. Previous studies on feline calicivirus and murine norovirus 1 (MNV1) demonstrated that the viral protein, genome-linked (VPg), acts to direct translation by hijacking the host protein synthesis machinery. Here we report that MNV1 infection modulates the MAPK pathway to activate eIF4E phosphorylation. Our results show that the activation of p38 and Mnk during MNV1 infection is important for MNV1 replication. Furthermore, phosphorylated eIF4E relocates to the polysomes, and this contributes to changes in the translational state of specific host mRNAs. We propose that global translational control of the host by eIF4E phosphorylation is a key component of the host-pathogen interaction.