CVB3诱导的P62裂变通过NRF2/GPX4轴促进铁亡,并促进病毒复制
Feng He1, Zhuo Liu1, Miao Feng1
1Department of Biochemistry and Immunology, Capital Center for Children's Health, Capital Medical University, Capital Institute of Pediatrics, Beijing, China.
Frontiers in microbiology
|December 8, 2025
概括
考克萨基病毒B3 (CVB3) 通过裂解P62引起病毒性心肌炎,这使KEAP1/NRF2/GPX4通路失活,并促进铁亡. 恢复P62功能或补充可以治疗CVB3诱导的疾病.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 病变的发生和发病.
背景情况:
- 考克萨基病毒B3 (CVB3) 是病毒性心肌炎的关键原因,导致显著的组织损伤.
- 关联CVB3感染与ferroptosis (一种受调节的细胞死亡形式) 的分子机制尚未完全理解.
研究的目的:
- 阐明CVB3诱导病理效应的分子途径,重点关注铁亡.
- 研究选择性自受体P62和KEAP1/NRF2/GPX4轴在CVB3病变发生中的作用.
主要方法:
- 使用CVB3感染的体外和体外模型.
- 采用免疫阻塞,基因操纵和病毒分析来研究P62处理.
- 使用不可切割的P62突变体检查KEAP1/NRF2/GPX4轴,并评估感染小鼠的补充剂.
主要成果:
- CVB3复制导致P62裂变,促进NRF2降解和GPX4下调,从而诱导铁亡.
- 一种不可切割的P62突变稳定了KEAP1/NRF2/GPX4通路,减少了细胞和动物模型中的铁亡.
- 富含的饮食补充剂抑制了铁亡并改善了CVB3感染小鼠的存活率.
结论:
- 通过P62裂变,CVB3使KEAP1/NRF2/GPX4轴失活,从而导致铁亡和疾病进展.
- 恢复P62功能和补充剂代表了CVB3诱导病变的潜在治疗策略.
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