黑鱼Nup93可以负面调节IRF3和IRF7介导的抗病毒免疫反应
Zhan'ao Li1, Xinyu Wang1, Shasha Tan1
1State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha, China.
Journal of immunology (Baltimore, Md. : 1950)
|October 23, 2025
概括
黑鱼中的核素93 (Nup93) 通过降低IRF3/7蛋白水平来抑制抗病毒免疫力. 这项研究揭示了Nup93的存在.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 病毒学 病毒学
背景情况:
- 核素93 (Nup93) 是核孔复合物的组成部分,参与细胞过程,包括免疫信号传递.
- 在哺乳动物中,Nup93积极调节视网膜酸诱导基因I (RLR) 信号通路.
- 目前,Nup93在远距离免疫力,特别是鱼类中的功能基本上是未知的.
研究的目的:
- 在黑鱼中克隆和描述Nup93同类物 (bcNup93) .
- 研究bcNup93在黑鱼的抗病毒免疫反应中的作用.
- 阐明bcNup93在抗病毒免疫中的功能背后的分子机制.
主要方法:
- 黑鱼Nup93 (bcNup93) 的克隆和序列分析.
- 定量RT-PCR用于分析bcNup93mRNA表达.
- 免疫涂抹,免疫光和核细胞体分离用于蛋白质分析和定位.
- 在细胞培养和幼鱼中对bcNup93 Knockdown进行RNA干扰 (RNAi).
- 对干扰素和干扰素刺激的基因表达,病毒载量和生存率的分析.
- 同免疫沉和无处不在测试用于研究蛋白质相互作用和降解途径.
主要成果:
- bcNup93被克隆和表征,显示典型的Nup93域 (卷轴和NIC96).
- bcNup93 mRNA水平在病毒和多I:C刺激后波动.
- bcNup93局部化到核外,其敲击增强了干扰素生产和抗病毒能力.
- 在鱼类中抑制bcNup93减少了病毒基因表达,改善了生存率.
- bcNup93与bcIRF3 / 7相互作用,促进它们的溶酶体降解,并通过K63链接的无化降低它们的稳定性和活性.
结论:
- bcNup93负面调节黑鱼的抗病毒免疫反应.
- 这种抑制是通过通过溶酶体降解减弱bcIRF3/7蛋白水平来实现的.
- 对于bcNup93在抗病毒信号传递中的抑制功能来说,bcNup93的线圈和NIC96域都至关重要.
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