Zika virus inhibits eIF2α-dependent stress granule assembly.
Zika virus inhibits eIF2α-dependent stress granule assembly.
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DOI：
10.1371/journal.pntd.0005775
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发表时间：
2017-07
影响因子：
3.8
通讯作者：
Mouland AJ
中科院分区：
文献类型：
--
作者：
Amorim R;Temzi A;Griffin BD;Mouland AJ
寨卡病毒（ZIKV）是黄病毒科的一员，是最新出现的具有大流行潜力的虫媒病毒。在感染过程中，病毒触发宿主细胞应激反应，导致 RNA 翻译发生变化，并组装大量停滞的翻译前启动复合物，称为应激颗粒 (SG)。一些报告表明黄病毒调节应激颗粒（SG）的组装。作为一种新兴病原体，人们对 ZIKV 如何调节宿主细胞应激反应知之甚少。在这项工作中，我们研究了 ZIKV 如何调节 SG 组装。我们证明，ZIKV 在亚砷酸钠 (Ars) 诱导的氧化应激条件下会对 SG 组装产生负面影响，亚砷酸钠 (Ars) 是一种导致 eIF2α 磷酸化的处理方法。相比之下，在用亚硒酸钠 (Se) 或 Pateamine A (PatA)（触发 eIF2α 独立的 SG 组装的化合物）处理的模拟细胞和 ZIKV 感染细胞之间，没有观察到 SG 组装的可测量差异。有趣的是，ZIKV 感染显着损害了 Ars 处理的感染细胞中触发的 eIF2α 磷酸化，并且 ZIKV 感染细胞中 SG 组装的废除至少部分依赖于 eIF2α 去磷酸化。这些数据表明，ZIKV 能够引发抵消宿主抗病毒应激反应的机制，从而促进有利于病毒复制的细胞环境。寨卡病毒（ZIKV）主要通过蚊虫叮咬传播给人类，但也存在性传播、围产期传播和疑似输血传播的病例。它与胎儿畸形和成人神经系统疾病有关。人们对这种病原体的日益关注导致世界卫生组织宣布其为国际关注的神经系统疾病突发公共卫生事件。全球正在进行一项紧急科学努力，以更好地了解 ZIKV 生物学并定义病毒与宿主细胞之间发生的相互作用。我们评估了 ZIKV 感染如何抵消称为应激颗粒 (SG) 的 RNA 和蛋白质动态聚集体的组装。我们观察到 ZIKV 阻断亚砷酸钠 (Ars) 诱导的 SG 组装，但不阻断亚硒酸钠或 Pateamine A 诱导的 SG 组装。我们证明这种差异与 ZIKV 通过其磷酸酶调节 eIF2α 去磷酸化的能力有关。我们的工作表明，ZIKV 可防止宿主应激反应，以维持有利于病毒复制的细胞环境。
Zika virus (ZIKV), a member of the Flaviviridae family, is the most recent emerging arbovirus with pandemic potential. During infection, viruses trigger the host cell stress response, leading to changes in RNA translation and the assembly of large aggregates of stalled translation preinitiation complexes, termed stress granules (SGs). Several reports demonstrate that flaviviruses modulate the assembly of stress granules (SG). As an emerging pathogen, little is known however about how ZIKV modulates the host cell stress response. In this work, we investigate how ZIKV modulates SG assembly. We demonstrate that ZIKV negatively impacts SG assembly under oxidative stress conditions induced by sodium arsenite (Ars), a treatment that leads to the phosphorylation of eIF2α. By contrast, no measurable difference in SG assembly was observed between mock and ZIKV-infected cells treated with sodium selenite (Se) or Pateamine A (PatA), compounds that trigger eIF2α-independent SG assembly. Interestingly, ZIKV infection markedly impaired the phosphorylation of eIF2α triggered in Ars-treated infected cells, and the abrogation of SG assembly in ZIKV-infected cells is, at least in part, dependent on eIF2α dephosphorylation. These data demonstrate that ZIKV elicits mechanisms to counteract host anti-viral stress responses to promote a cellular environment propitious for viral replication. Zika virus (ZIKV) is transmitted to humans primarily through mosquito bites, but there have also been cases of sexual, perinatal, and suspected blood transfusion transmission. It has been associated with fetal malformations and neurological disorders in adults. The rising concern about this pathogen led the World Health Organization to declare it as a public health emergency of international concern regarding neurological disorders. There is an urgent global scientific effort underway to better understand ZIKV biology and define interactions that occur between the virus and the host cell. We evaluated how ZIKV infection counteracts the assembly of dynamic aggregates of RNA and proteins called stress granules (SGs). We observed that ZIKV blocks SG assembly induced by sodium arsenite (Ars), but not by sodium selenite or Pateamine A. We demonstrate that this difference is related to the ability of ZIKV to modulate the dephosphorylation of eIF2α via its phosphatase. Our work demonstrates that ZIKV prevents a host stress response in order to maintain a cellular environment propitious for viral replication.
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DOI：
10.1073/pnas.0703348104
发表时间：
2007-05-22
影响因子：
11.1
作者：
Emara, Mohamed M.;Brinton, Margo A.
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影响因子：
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DOI：
10.1126/science.aaf8160
发表时间：
2016-08-12
期刊：
Science (New York, N.Y.)
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Rodriguez-Barraquer I
DOI：
10.1016/0035-9203(52)90042-4
发表时间：
1952-01-01
影响因子：
2.2
作者：
DICK, GWA;KITCHEN, SF;HADDOW, AJ
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HADDOW, AJ
DOI：
10.1083/jcb.147.7.1431
发表时间：
1999-12-27
期刊：
The Journal of cell biology
影响因子：
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作者：
Kedersha NL;Gupta M;Li W;Miller I;Anderson P
通讯作者：
Anderson P