STING激活ZBP1介导的PANoptosis,以防御HSV-1视网膜感染
Wei Liu1, Haifeng Cui1, Li Wang1
1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat- sen University, Guangzhou, 510060, China.
Journal of neuroinflammation
|October 28, 2025
概括
干扰素基因刺激器 (STING) 是通过激活Z-DNA结合蛋白1 (ZBP1) 介导的PANoptosis来控制简单疹病毒1型 (HSV-1) 视网膜感染的关键. 这一途径为病毒性视网膜炎提供了新的治疗点,如急性视网膜亡 (ARN).
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 眼科医生 眼科 眼科
背景情况:
- 简单疹病毒1型 (HSV-1) 导致传染性失明和急性视网膜亡 (ARN).
- 目前针对HSV-1视网膜感染的治疗方法缺乏特异性,并针对一般抗病毒机制.
- 干扰素基因刺激器 (STING) 是先天免疫的关键组成部分.
研究的目的:
- 调查STING在HSV-1视网膜感染中的作用.
- 阐明在视网膜中通过STING介导的抗病毒反应背后的分子机制.
- 探索针对病毒性视网膜炎的STING-ZBP1-PANoptosis轴的潜在治疗策略.
主要方法:
- 使用STING淘汰赛 (KO) 和ZBP1 KO小鼠模型来评估HSV-1视网膜感染的易感性.
- 分析了感染小鼠的免疫反应,病毒载荷和视网膜病理.
- 使用分子试验研究了STING与ZBP1和Z型核酸的相互作用.
- 在体外和体内评估ZBP1激动剂 (Curaxin CBL0137) 的治疗潜力.
主要成果:
- 丁科小鼠对HSV-1感染的敏感性增加,抗病毒免疫力受损,病毒载量较高,视网膜严重亡.
- 在HSV-1感染期间,STING对于微质和巨细胞中ZBP1介导的PANoptosis至关重要.
- STING激活导致Z型核酸的形成和随后的ZBP1激活.
- ZBP1 KO小鼠表现出与STING KO小鼠相似的抗病毒缺陷.
- 库拉辛CBL0137治疗挽救了STING缺乏细胞中的抗病毒反应,并在野生型和STING KO小鼠中缓解了视网膜亡.
结论:
- 一个新的STING-ZBP1-PANoptosis信号轴对于控制HSV-1视网膜感染至关重要.
- 这一途径代表了开发抗病毒视网膜炎治疗方法的有希望的新目标,包括RNA.
- 向ZBP1激活可能为管理HSV-1引起的眼病提供一种特定的治疗方法.
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