冠状病毒包膜蛋白激活TMED10介导的非传统的炎症因子分泌
Lei Liu1,2, Lijingyao Zhang1,3, Xinyan Hao1,2
1State Key Laboratory of Membrane Biology, Tsinghua University, Beijing, 100084, China.
Nature communications
|October 8, 2024
概括
严重的冠状病毒.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 在冠状病毒感染期间,炎症性细胞因子产量增加的机制尚未完全理解.
- 严重的冠状病毒 (SARS-CoV-2,SARS,MERS) 诱导显著的肺炎.
- 轻度冠状病毒 (229E,HKU1,OC43) 的炎症效应较小.
研究的目的:
- 为了确定严重的冠状病毒感染中增加的促炎性细胞因子产生背后的细胞机制.
- 为了研究包膜 (E) 蛋白在冠状病毒引起的炎症中的作用.
- 探索潜在的治疗点,以减轻冠状病毒引起的高炎症.
主要方法:
- 封面 (E) 蛋白的鉴定作为诱导因特鲁金-1释放的诱导剂.
- 研究TMED10介导的非传统蛋白质分泌 (UcPS) 在炎症中的作用.
- 分析严重冠状病毒E蛋白中的SS/DS基因及其与TMED10的相互作用.
- 使用小鼠肝炎病毒 (MHV) 感染模型来测试治疗化合物.
主要成果:
- 严重的冠状病毒的E蛋白质,与轻度菌株不同,含有SS/DS图案.
- 这个图案促进了与TMED10的相互作用,增强了TMED10-oligomerization和UcPS.
- 蛋白E激活TMED10介导的UcPS,导致白素-1释放量增加和肺炎.
- 在MHV模型中,发现孕激素类似物抑制了E增强的炎症因子释放,并减少了肺炎.
结论:
- E蛋白-TMED10相互作用是推动冠状病毒引起的高炎症的关键分子机制.
- 这种相互作用促进了interleukin-1非传统蛋白质分泌 (UcPS) 进入ER-Golgi中间区 (ERGIC).
- 针对E蛋白-TMED10相互作用提供了针对严重的冠状病毒炎症的潜在治疗策略.
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