AUP1和UBE2G2复合体针对STING信号,并调节病毒诱导的先天免疫力
Xin-Tao Wang1, Xi Zhu1, Zhong-Hao Lian1
1Hunan Provincial Key Laboratory of Medical Virology, Institute of Pathogen Biology and Immunology, College of Biology, Hunan University, Changsha, Hunan, China.
mBio
|April 16, 2025
概括
古代无处不在的蛋白质1 (AUP1) 负面调节STING信号,防止自发免疫激活. 缺少AUP1可以增强抗病毒免疫力,并抑制DNA和RNA病毒的复制.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 细胞生物学 细胞生物学
背景情况:
- 干扰素基因刺激器 (STING) 是对抗DNA病原体宿主防御的关键适应器.
- 精确调节STING对于免疫平衡和预防自身炎症至关重要.
- 维持STING静止状态的机制尚未完全理解.
研究的目的:
- 研究古代无处不在的蛋白1 (AUP1) 在调节STING信号传递中的作用.
- 阐明AUP1在先天免疫和病毒复制中的功能.
- 为了确定AUP1在脂质代谢途径中的参与.
主要方法:
- 在缺乏AUP1的细胞和生物体中研究了STING激活.
- 研究了AUP1,UBE2G2和STING之间的相互作用.
- 分析了DNA和RNA病毒在AUP1缺陷模型中的病毒复制.
- 检查了脂质滴滴积累和脂质代谢基因的表达.
主要成果:
- 缺乏AUP1导致自发性STING激活和增加I型干扰素的产生.
- 带有辅因子UBE2G2的AUP1与STING相互作用,将其保留在ER中.
- 缺少AUP1增强了STING介导的抗病毒反应,并赋予了对DNA病毒感染的抵抗力.
- 缺少AUP1通过减少脂质积累和改变脂质代谢基因表达来抑制RNA病毒 (VSV) 复制.
结论:
- AUP1 和 UBE2G2 作为 STING 信号的负调节器.
- AUP1保留了ER中的STING,阻止了它的激活,并限制了免疫反应.
- 通过调节STING信号和脂质代谢,AUP1在调节病毒复制方面发挥着双重作用.
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