特定物种IL-1β是塞内卡谷病毒3C蛋白酶的炎症传感器
Xiangyu Huang1,2, Zhenchao Zhao1,2, Cheng Zhu3
1National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China.
PLoS pathogens
|July 22, 2024
概括
猪的Pro-IL-1β,与其人类对应物不同,由病毒蛋白酶激活. 这揭示了一种独立于炎症体的新型炎症途径,突出了IL-1β作为直接的病毒传感器.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 结构生物学 结构生物学
背景情况:
- 炎症酶是炎症的关键调节者,处理像IL-1β这样的细胞因子.
- 卡斯帕酶-1成熟IL-1β,但其他IL-1β转化酶的机制尚不清楚.
- 人类卡斯巴-4处理IL-18,对Pro-IL-18激活的结构洞察力.
研究的目的:
- 阐明病毒蛋白酶对亲IL-1β激活的机制.
- 调查由塞内卡谷病毒 (SVV) 3C蛋白酶对猪亲IL-1β进行选择性切割的结构基础.
- 为了确定IL-1β激活的替代途径,独立于炎症体.
主要方法:
- 猪和人类亲IL-1β结构和加工的比较分析.
- 使用SVV 3C蛋白酶进行酶分裂试验.
- 分子建模和突变发生研究.
- 对猪膜巨细胞 (PAMs) 的实验.
主要成果:
- 猪的Pro-IL-1β (sPro-IL-1β) 存在于一个寡合体前体,不同于单体的人类Pro-IL-1β (hPro-IL-1β).
- SVV 3C 蛋白酶有效地分裂sPro-IL-1β以产生成熟的IL-1β,但不是hPro-IL-1β.
- sPro-IL-1β的前域充当"外位体",通过疏水相互作用将其引导到SVV 3C蛋白酶活性部位.
- 由SVV 3C蛋白酶激活IL-1β发生的独立于PAMs中的炎症体信号传递.
结论:
- 猪IL-1β作为炎症传感器,直接检测病毒蛋白酶.
- 对于IL-1β激活的新途径存在于宿主炎症体的并行中.
- 这种病毒蛋白酶介导的激活途径为抗炎和抗病毒策略提供了新的点.
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