Newcastle disease virus induces stable formation of bona fide stress granules to facilitate viral replication through manipulating host protein translation
Newcastle disease virus induces stable formation of bona fide stress granules to facilitate viral replication through manipulating host protein translation
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新城疫病毒诱导真正应激颗粒的稳定形成，通过操纵宿主蛋白翻译促进病毒复制
DOI：
10.1096/fj.201600980r
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发表时间：
2017-04-01
期刊：
影响因子：
4.8
通讯作者：
Ding, Chan
中科院分区：
文献类型：
--
作者：
Sun, Yingjie;Dong, Luna;Ding, Chan
哺乳动物细胞通过抑制细胞质mRNA、蛋白质翻译元件和RNA结合蛋白来响应各种环境应激因子形成应激颗粒（SGs）。根据病毒的种类，病毒诱导的SGs以不同的方式起作用；然而，病毒复制的调控机制尚不清楚。在本研究中，新城疫病毒（NDV）通过激活蛋白激酶R (PKR)/eIF2a通路，在HeLa细胞上触发了真实SGs的稳定形成。ndv诱导的SGs含有典型的sgg标记物t细胞内抗原（TIA）（-1）、rasgtpase激活蛋白结合蛋白（G3BP）（-1）、真核起始因子和小的核糖体亚基，这些亚基在环己亚胺存在下可被分解。用微管阻断药物诺可达唑治疗可形成相对较小的圆形颗粒，表明NDV感染可诱导典型SGs。此外，通过敲低HeLa细胞SG形成的关键组分TIA（-1）和TIA（-1）相关（TIAR）蛋白，研究了SGs在NDV复制中的作用。结果表明，缺失TIA-1 ortita抑制了病毒蛋白的合成，降低了外胞病毒的产量，但增加了全局蛋白翻译。FISH显示ndv诱导的SGs主要含有细胞mRNA而不是病毒mRNA。TIA（-1）或TIAR的缺失降低了多体中的NP mRNA水平。这些结果表明，新冠病毒可以触发稳定的抗原esg的形成，通过抑制细胞mrna，有利于病毒蛋白的翻译和病毒的复制。-孙艳，董丽，于生，王晓燕，郑海，张鹏，孟，C，詹艳，谭丽，宋春春，邱晓霞，王刚，廖，艳，丁超。新城疫病毒通过操纵宿主蛋白翻译诱导真实胁迫颗粒的稳定形成，促进病毒复制。
Mammalian cells respond to various environmental stressors to form stress granules (SGs) by arresting cytoplasmic mRNA, protein translation element, and RNA binding proteins. Virus-induced SGs function in different ways, depending on the species of virus; however, themechanismofSGregulation of virus replication is not well understood. In this study, Newcastle disease virus (NDV) triggered stable formation of bona fide SGs on HeLa cells through activating the protein kinase R (PKR)/eIF2a pathway. NDV-induced SGs contained classic SGmarkers T-cell internal antigen (TIA)(-1), RasGTPase-activatingprotein-binding protein (G3BP)(-1), eukaryotic initiation factors, andsmall ribosomal subunit, which could be disassembled in the presence of cycloheximide. Treatment with nocodazole, amicrotubule disruptiondrug, led to the formation of relatively small and circular granules, indicating that NDV infection induces canonical SGs. Furthermore, the role of SGs on NDV replication was investigated by knockdown of TIA(-1) and TIA(-1)-related (TIAR) protein, the 2 critical components involved in SG formation from the HeLa cells, followed by NDV infection. Results showed that depletion of TIA-1 orTIARinhibitedviral protein synthesis, reducedextracellularvirus yields, but increasedglobal protein translation. FISH revealed that NDV-induced SGs contained predominantly cellular mRNA rather than viral mRNA. Deletion of TIA(-1) or TIAR reduced NP mRNA levels in polysomes. These results demonstrate that NDV triggers stable formationofbonafideSGs, whichbenefit viralprotein translation andvirus replicationbyarresting cellularmRNA.-Sun, Y., Dong, L., Yu, S., Wang, X., Zheng, H., Zhang, P., Meng, C., Zhan, Y., Tan, L., Song, C., Qiu, X., Wang, G., Liao, Y., Ding, C. Newcastle disease virus induces stable formation of bona fide stress granules to facilitate viral replication through manipulating host protein translation.