沙门类双链RNA依赖蛋白激酶激活了亡并抑制了蛋白质合成
Lise Chaumont1, Mathilde Peruzzi1, François Huetz2
1Université Paris-Saclay, INRAE, UVSQ, VIM, Jouy-en-Josas, France.
Journal of immunology (Baltimore, Md. : 1950)
|July 26, 2024
概括
鱼类蛋白激酶R (PKR) 具有保存的抗病毒功能,包括诱导亡和翻译抑制. 然而,像VHSV这样的病毒采用策略来逃避这些天生的免疫反应.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 鱼类病毒学 病毒学
背景情况:
- 蛋白激酶R (PKR) 是先天免疫系统的关键组成部分,通过翻译抑制和亡来调解抗病毒反应.
- 了解PKR抗病毒功能的进化保存对于理解宿主-病原体相互作用至关重要.
研究的目的:
- 研究鱼类PKR在鱼 (Oncorhynchus tshawytscha) 中的作用和保存的抗病毒功能.
- 描述不同的鱼类PKR异型及其在抗病毒防御机制中的参与.
主要方法:
- 三种不同的鱼PKR mRNA异型 (PKR-FL,PKR-ML,PKR-SL) 的克隆和特征.
- 使用CRISPR/Cas9基因组编辑开发了一种缺乏PKR的 (pkr-/-) 奇诺克鱼细胞系.
- 过度表达和淘汰赛研究,以评估PKR的功能,以响应IFNA2刺激和病毒性出血性败血症病毒 (VHSV) 感染.
主要成果:
- 含有dsRNA结合和激酶域的PKR-FL显示出抗病毒功能,包括亡激活和蛋白质合成抑制.
- 在晚期VHSV感染期间,PKR淘汰细胞显示出受损的亡,证实了PKR的作用.
- 内源性PKR介导的翻译抑制在多种I:C传染时发生,但在VHSV感染期间没有发生.
- PKR并没有直接抑制病毒复制,但似乎通过触发晚期亡来促进病毒释放.
结论:
- 鱼类PKR具有对抗病毒防御至关重要的保存的分子功能.
- 像VHSV这样的病毒已经发展出规避鱼类PKR介导免疫力的策略.
- 通过晚期亡促进病毒释放的PKR作用突出显示了宿主防御和病毒传播之间的复杂相互作用.
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