Le Sage Valerie, Cinti Alessandro, McCarthy Stephen, Amorim Raquel, Rao Shringar, Daino Gian Luca, Tramontano Enzo, Branch Donald R, Mouland Andrew J
HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montréal, Québec, Canada H3T 1E2.
HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montréal, Québec, Canada H3T 1E2; Department of Medicine, McGill University, Montréal, Québec, Canada H3A 0G4.
Virology. 2017 Feb;502:73-83. doi: 10.1016/j.virol.2016.12.012. Epub 2016 Dec 23.
Stress granules (SGs) are dynamic cytoplasmic aggregates of translationally silenced mRNAs that assemble in response to environmental stress. SGs appear to play an important role in antiviral innate immunity and many viruses have evolved to block or subvert SGs components for their own benefit. Here, we demonstrate that intracellular Ebola virus (EBOV) replication and transcription-competent virus like particles (trVLP) infection does not lead to SG assembly but leads to a blockade to Arsenite-induced SG assembly. Moreover we show that EBOV VP35 represses the assembly of canonical and non-canonical SGs induced by a variety of pharmacological stresses. This SG blockade requires, at least in part, the C-terminal domain of VP35. Furthermore, results from our co-immunoprecipitation studies indicate that VP35 interacts with multiple SG components, including G3BP1, eIF3 and eEF2 through a stress- and RNA-independent mechanism. These data suggest a novel function for EBOV VP35 in the repression of SG assembly.
应激颗粒（SGs）是翻译沉默的mRNA在细胞质中动态聚集形成的，其在环境应激反应时组装。应激颗粒似乎在抗病毒天然免疫中发挥重要作用，许多病毒已经进化出阻断或颠覆应激颗粒成分以利于自身的机制。在此，我们证明细胞内埃博拉病毒（EBOV）复制及具有转录能力的病毒样颗粒（trVLP）感染不会导致应激颗粒组装，但会导致对亚砷酸盐诱导的应激颗粒组装产生阻断作用。此外，我们表明埃博拉病毒VP35蛋白可抑制由多种药理应激诱导的典型和非典型应激颗粒的组装。这种对应激颗粒的阻断至少部分需要VP35的C末端结构域。此外，我们的免疫共沉淀研究结果表明，VP35通过一种不依赖应激和RNA的机制与多种应激颗粒成分相互作用，包括G3BP1、eIF3和eEF2。这些数据表明埃博拉病毒VP35蛋白在抑制应激颗粒组装方面具有新功能。
