普雷福丁复合物促进干扰素刺激的基因表达,并被轮状病毒VP3抑制
Yinxing Zhu1, Yanhua Song2,3, Dilip Kumar4,5
1Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
Nature communications
|August 29, 2025
概括
通过抑制干扰素刺激基因 (ISG) 表达至关重要的前foldin-UBA3复合体,破坏宿主抗病毒防御. 这种相互作用削弱了对病毒感染的免疫反应.
科学领域:
- 病毒学
- 免疫学
- 分子生物学
背景情况:
- 干扰素 (IFN) 和干扰素刺激基因 (ISG) 对宿主抗病毒的防御至关重要.
- 众所周知,罗塔病毒蛋白VP3对干扰素反应起作用,但其机制尚不清楚.
研究的目的:
- 阐明罗塔病毒VP3对宿主抗病毒免疫力的分子机制.
- 识别与轮状病毒VP3相互作用的细胞蛋白.
主要方法:
- 与高分辨率质谱相结合的双联亲和净化,以确定VP3结合伙伴.
- 无标签的全蛋白质量测量以分析蛋白质表达的变化.
- 在prefoldin亚单元淘汰细胞中分析轮状病毒感染.
主要成果:
- 预福丁复合物被确定为罗塔病毒VP3的关键细胞结合伙伴.
- 甲素子单元的淘汰显著增强了轮状病毒感染.
- 普雷福丁促进了UBA3的折叠 (类似于ubiquitin的修饰激活酶3),从而积极调节ISG的表达.
- 罗塔病毒VP3直接结合于前foldin,抑制其伴侣活性,导致UBA3的不稳定性,降低IRF9,并抑制ISG转录.
结论:
- 报告了一种对抗病毒免疫性至关重要的新型前素- UBA3- IRF9- ISG轴.
- 罗塔病毒VP3通过破坏这个轴来对抗宿主免疫力.
- 这些发现为广泛的抗病毒疗法开发提供了潜在的目标.
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