Department of Microbiology and Immunology, Dalhousie University, 5850 College Street, Halifax NS, Canada.
FASEB J. 2012 Apr;26(4):1629-39. doi: 10.1096/fj.11-196915. Epub 2011 Dec 27.
An important component of the mammalian stress response is the reprogramming of translation. A variety of stresses trigger abrupt polysome disassembly and the accumulation of stalled translation preinitiation complexes. These complexes nucleate cytoplasmic stress granules (SGs), sites of mRNA triage in which mRNAs from disassembling polysomes are sorted and the fates of individual transcripts are determined. Here, we demonstrate that influenza A virus (IAV) actively suppresses SG formation during infection, thereby allowing translation of viral mRNAs. Complete inhibition of SG formation is dependent on the function of the viral nonstructural protein 1 (NS1); at late times postinfection, cells infected with NS1-mutant viruses formed SGs in a double-stranded RNA-activated protein kinase (PKR)-dependent fashion. In these cells, SG formation correlated with inhibited viral protein synthesis. Together, these experiments demonstrate the antiviral potential of SGs and reveal a viral countermeasure that limits SG formation.
哺乳动物应激反应的一个重要组成部分是翻译的重编程。各种应激源触发多核糖体解体和翻译起始复合物的积累。这些复合物启动细胞质应激颗粒（SG），mRNA 分类的部位，来自解体多核糖体的 mRNA 被分类，并且单个转录本的命运被确定。在这里，我们证明甲型流感病毒（IAV）在感染过程中积极抑制 SG 的形成，从而允许病毒 mRNA 的翻译。SG 形成的完全抑制依赖于病毒非结构蛋白 1（NS1）的功能；在感染后晚期，用 NS1 突变病毒感染的细胞以双链 RNA 激活蛋白激酶（PKR）依赖性方式形成 SG。在这些细胞中，SG 的形成与抑制病毒蛋白合成相关。这些实验共同证明了 SG 的抗病毒潜力，并揭示了一种限制 SG 形成的病毒对策。
