I型/III型IFN和相关因素调节JEV感染和BBB内皮完整性
Ya-Ge Zhang1,2,3, Hong-Xin Zhang1,2,3, Hao-Wei Chen1,2,3
1State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.
Journal of neuroinflammation
|September 26, 2023
概括
日本脑炎病毒 (JEV) 破坏了血脑屏障 (BBB). I/III型干扰素 (IFN) 和相关因素调节BBB完整性,限制JEV感染,为日本脑炎 (JE) 提供潜在的治疗策略.
科学领域:
- 神经病毒学 神经病毒学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 日本脑炎病毒 (JEV) 引起日本脑炎 (JE),其特征是血脑屏障 (BBB) 破坏和中枢神经系统炎症.
- 确切的JEV病变机制,特别是它与大脑微血管内皮细胞 (BMEC) 和BBB的相互作用,仍然不清楚.
- I/III型干扰素 (IFN) 在JE病原和BBB完整性中的作用是模两可的.
研究的目的:
- 阐明在JEV感染期间人类BMECs (hBMECs) 中宿主-病原体相互作用的分子机制.
- 调查免疫因子,包括IFN和干扰素诱导蛋白 (IFIT) 在调节JEV挑战下BBB完整性的作用.
- 基于宿主-病原体相互作用,探索日本脑炎的潜在治疗点.
主要方法:
- RNA测序 (RNA-seq) 用于对JEV感染的hBMECs中的基因表达变化进行分析.
- 定量PCR,ELISA和西式涂抹分析基因和蛋白质表达.
- 试验室模型,包括shRNA介导的淘汰和跨井BBB模型,以评估免疫因子功能和BBB完整性.
主要成果:
- 疹病毒感染显著改变了hBMECs中的基因表达,影响了抗病毒防御和内皮细胞泄漏途径.
- 模式识别受体 (PRRs) 感知了JEV,启动了IRF/IFN信号,从而通过四三重复 (IFITs) 调节了干扰素诱导的蛋白质.
- 类型I/III的IFN稳定了内皮屏障,而IFIT被发现对IFN介导的屏障维护是不必要的.
结论:
- 这项研究提供了在JEV入侵期间hBMECs宿主-病原体相互作用的全面分子理解.
- I/III型IFN和相关因素在调节hBMEC屏障和限制JEV感染方面发挥着至关重要的作用.
- 这些发现表明,对治疗日本脑炎有希望的治疗策略.
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