通过EIF2S1-ATF4-PRKN通路抑制线粒细胞衰变有助于病毒性脑炎
Xiaowei Song1, Yiliang Wang2, Weixiangmin Zou3
1Institute of Biomedicine, College of Life Science and Technology, Guangdong Province Key Laboratory of Bioengineering Medicine, Key Laboratory of Innovative Technology Research on Natural Products and Cosmetics Raw Materials, Jinan University, Guangzhou 510632, China; Center for Mitochondrial Genetics and Health, Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou 511400, China.
Journal of advanced research
|August 5, 2024
概括
线粒体,一个清除受损线粒体的过程,受到简单疹病毒1 (HSV-1) 感染的损害,恶化简单疹脑炎 (HSE). 激活线粒能保护HSV-1病毒,可能是一种新的抗病毒疗法.
科学领域:
- 神经病毒学 神经病毒学
- 线粒体生物学 线粒体生物学
- 免疫学 免疫学 免疫学
背景情况:
- 线粒体菌维持线粒体的健康,并影响抗病毒免疫力.
- 简单疹病毒1 (HSV-1) 感染和脑炎 (HSE) 涉及与细胞过程的复杂相互作用.
- 线粒在HSV-1感染和HSE中的作用尚不清楚.
研究的目的:
- 在HSV-1神经向性感染期间调查线粒细胞的调节.
- 确定米托法基在病毒性脑炎的发病过程中的作用.
- 确定调节线粒的化合物,以影响HSV-1感染.
主要方法:
- 使用了西方斑点,RT-PCR,斑块检测和传输电子显微镜 (TEM).
- 评估了帕金 (PRKN) 介导的神经和核因子卡帕B (NFKB) 介导的神经炎症.
- 采用了体外和体内模型,包括用氨酸或PRKN过度表达治疗的HSE小鼠模型.
主要成果:
- HSV-1 感染最初会激活线粒,但后来通过通过病毒蛋白 ICP34.5/US11.5 抑制PRKN 表达来抑制它.
- 抑制线粒细胞衰变会增强HSV-1感染,而激活线粒细胞衰变 (通过PRKN过度表达或激动剂) 会减少病毒载量和神经炎症.
- 氨酸是一种肠道代谢物,通过促进PRKN的表达来激活细胞,从而在体外和体内限制HSV-1感染.
结论:
- 线性菌在简单疹脑炎 (HSE) 病变发生过程中起着保护作用.
- 激活线粒是一种有前途的抗病毒治疗策略,用于HSV-1相关疾病.
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