遗传 ›› 2019, Vol. 41 ›› Issue (6): 494-508.doi: 10.16288/j.yczz.19-020

• 综述 • 上一篇    下一篇

应激颗粒与病毒的相互制约

黄羽,胡斯奇,郭斐()   

  1. 中国医学科学院/北京协和医学院病原生物学研究所,国家卫生健康委员会病原系统生物学重点实验室,北京 100730
  • 收稿日期:2019-03-07 修回日期:2019-05-15 出版日期:2019-06-20 发布日期:2019-05-23
  • 作者简介:黄羽,博士研究生,专业方向:病毒与宿主限制因子相互作用。E-mail: huangyu910730@163.com
  • 基金资助:
    国家重点研发计划项目资助(2016YFD0500307FF09)

Interaction between stress granules and viruses

Yu Huang,Siqi Hu,Fei Guo()   

  1. NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
  • Received:2019-03-07 Revised:2019-05-15 Published:2019-06-20 Online:2019-05-23
  • Supported by:
    Supported by the National Key Plan for Scientific Research and Development of China(2016YFD0500307FF09)

摘要:

哺乳动物细胞受到热休克、氧化应激、营养缺乏或者病毒感染等环境压力时,能够迅速启动细胞的压力应答机制,终止细胞内的蛋白翻译,形成应激颗粒(stress granules, SGs)。SGs作为胞浆中翻译起始复合物的聚集产物,在细胞的基因表达和稳态中发挥着重要的作用,与细胞凋亡以及核功能具有密切联系。尤其是当病毒感染细胞时,SGs的形成可以使细胞内病毒蛋白翻译水平大大降低,从而抑制入侵病毒的复制。然而,病毒在长期进化过程中也衍生出了对抗细胞压力应答的相应机制,如与SGs关键组分相互作用,甚至切割等方式。本文对SGs的组成及诱发机制,特别是多种病毒诱导eIF2α磷酸化促成SGs组装的机制,以及病毒进化过程中形成的应对措施等方面进行了综述,旨在进一步阐释病毒感染与应激颗粒形成之间的相互影响和调控,为人们深入理解人体先天性免疫防御提供参考。

关键词: 应激颗粒, 翻译阻滞, 病毒, 先天性免疫

Abstract:

Stress granule (SG) formation is a primary mechanism through which gene expression is rapidly modulated when the eukaryotic cells undergo cellular stresses (including heat shock, oxidative stress, starvation, viral infection). SGs have been proposed to affect mRNA translation and stability, as well as being linked to apoptosis and nuclear processes. Formation of SGs after viral infection result in blockade of viral protein synthesis and viral replication. Not surprisingly, viruses from diverse families have been found to modulate SG formation in infected cells by associating with important SG effector proteins. Here we provide a summary of the current understanding of the mechanism of SG formation, describe the current knowledge on viruses induce and/or modulate SGs in infected cells via phosphorylation of eIF2α, and regulation of SGs in virus systems. Further, we summarize recent progresses in understanding the relationship between viruses and stress granules in mammalian cells, and suggest that SG formation is an important aspect of the antiviral innate immune response.

Key words: stress granules, translation arrest, virus, innate immunity