Importance of eIF2α phosphorylation assembly in alphavirus translation and stress granule regulation
Importance of eIF2α phosphorylation assembly in alphavirus translation and stress granule regulation
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DOI：
10.1091/mbc.e05-02-0124
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发表时间：
2005-08-01
影响因子：
3.3
通讯作者：
Liljeström, P
中科院分区：
文献类型：
--
作者：
McInerney, GM;Kedersha, NL;Liljeström, P
甲病毒感染导致宿主蛋白质合成的关闭，有利于病毒翻译。在这里，我们表明，在塞姆利基森林病毒（SFV）感染，翻译抑制主要是由于激活的细胞应激反应，通过磷酸化的真核翻译起始因子2 α亚基（eIF 2 α）。感染表达eIF 2a非磷酸化突变体的小鼠胚胎成纤维细胞（MEF）不会导致有效的关闭，尽管有效的病毒蛋白生产。此外，我们表明，SFV翻译增强子元件抵消了eIF 2a磷酸化所施加的翻译抑制。在野生型MEFs中，病毒感染诱导瞬时形成含有细胞TIA-1/R蛋白的应激颗粒（SG）。这些SG在病毒RNA复制附近被分解，与从细胞到病毒基因表达的转换同步。我们认为eIF 2a的磷酸化和随后的SG组装对于关闭的发生是重要的，并且局部SG拆卸和增强子的存在有助于SFV mRNA逃避一般的翻译停滞。
Alphavirus infection results in the shutoff of host protein synthesis in favor of viral translation. Here, we show that during Semliki Forest virus (SFV) infection, the translation inhibition is largely due to the activation of the cellular stress response via phosphorylation of eukaryotic translation initiation factor 2 alpha subunit (eIF2 alpha). Infection of mouse embryo fibroblasts (MEFs) expressing a nonphosphorylatable mutant of eIF2a does not result in efficient shutoff, despite efficient viral protein production. Furthermore, we show that the SFV translation enhancer element counteracts the translation inhibition imposed by eIF2a phosphorylation. In wild-type MEFs, viral infection induces the transient formation of stress granules (SGs) containing the cellular TIA-1/R proteins. These SGs are disassembled in the vicinity of viral RNA replication, synchronously with the switch from cellular to viral gene expression. We propose that phosphorylation of eIF2a and the consequent SG assembly is important for shutoff to occur and that the localized SG disassembly and the presence of the enhancer aid the SFV mRNAs to elude general translational arrest.