Amorim Raquel, Temzi Abdelkrim, Griffin Bryan D, Mouland Andrew J
Lady Davis Institute at the Jewish General Hospital, Montréal, Québec, Canada.
Department of Medicine, Division of Experimental Medicine, McGill University, Montréal, Québec, Canada.
PLoS Negl Trop Dis. 2017 Jul 17;11(7):e0005775. doi: 10.1371/journal.pntd.0005775. eCollection 2017 Jul.
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.
寨卡病毒（ZIKV）是黄病毒科的成员，是最近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，并形成大量停滞的翻译起始前复合物聚集体，即应激颗粒（SGs）。多项报告表明，黄病毒可调节应激颗粒（SG）的组装。然而，作为一种新兴病原体，关于寨卡病毒如何调节宿主细胞应激反应却知之甚少。在这项研究中，我们探究了寨卡病毒如何调节应激颗粒的组装。我们证明，在亚砷酸钠（Ars）诱导的氧化应激条件下，寨卡病毒对应激颗粒的组装产生负面影响，亚砷酸钠处理会导致真核生物翻译起始因子2α（eIF2α）磷酸化。相比之下，在用亚硒酸钠（Se）或茴香霉素A（PatA）处理的mock感染细胞和寨卡病毒感染细胞之间，未观察到应激颗粒组装有可测量的差异，亚硒酸钠和茴香霉素A是触发不依赖eIF2α的应激颗粒组装的化合物。有趣的是，寨卡病毒感染显著损害了经亚砷酸钠处理的感染细胞中触发的eIF2α磷酸化，并且寨卡病毒感染细胞中应激颗粒组装的消除至少部分取决于eIF2α的去磷酸化。这些数据表明，寨卡病毒引发了对抗宿主抗病毒应激反应的机制，以促进有利于病毒复制的细胞环境。
