群组TIM-1通过抑制免疫和炎症反应来促进诺达病毒感染
Long Lin1, Yin Zhao1, Yiting Ma1
1College of Marine Sciences, South China Agricultural University, Guangzhou, China.
Fish & shellfish immunology
|August 8, 2024
概括
色斑点的T细胞/跨膜免疫球蛋白和粘素域含有蛋白1 (TIM-1) 通过抑制免疫反应,促进红斑点神经亡病毒 (RGNNV) 感染. 这项研究揭示了TIM-1的存在.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 鱼类 水产养殖 水产养殖
背景情况:
- 含有T细胞/跨膜免疫球蛋白和粘素域 (TIM) 的蛋白质家族在免疫调节和病毒感染反应中起着至关重要的作用.
- 该家族的关键成员TIM-1与病毒病原发生有关,但其在鱼类诺达病毒感染期间的特定功能在很大程度上仍未被探索.
- 了解鱼类的免疫反应对于水产养殖健康和疾病管理至关重要.
研究的目的:
- 在色斑点 (Epinephelus coioides) 中识别和描述一种新的TIM-1同类物 (EcTIM-1).
- 研究EcTIM-1在对红斑神经亡病毒 (RGNNV) 感染的先天免疫反应中的作用.
- 阐明EcTIM-1影响病毒复制和宿主免疫信号的分子机制.
主要方法:
- 从色斑点鱼中识别和对EcTIM-1的序列分析.
- 定量实时PCR (qRT-PCR) 用于评估在各种组织和RGNNV挑战时的EcTIM-1表达.
- 在体外研究中使用异位表达来分析EcTIM-1对病毒复制和免疫路径激活的影响 (IFN,ISRE,NF-κB).
- 路西法酶记者试验评估了EcTIM-1对关键免疫信号分子 (MDA5,MAVS,STING,TBK1) 的影响.
主要成果:
- 鉴定了EcTIM-1,一种具有免疫球蛋白域的217氨基酸蛋白,并显示出对鱼和人类TIM-1的高度同质性.
- 在所有测试组织中检测到ecTIM-1表达,在对RGNNV感染的反应中显著上调.
- 过度表达EcTIM-1增强了RGNNV复制,并抑制了I型干扰素 (IFN1),干扰素刺激反应元件 (ISRE) 和核因子kappa-B (NF-κB) 促进物的活性.
- EcTIM-1抑制了IFN和炎症基因转录,并抑制了MDA5,MAVS,STING和TBK1激活的信号通路.
结论:
- EcTIM-1 作为色斑点的干扰素和炎症反应的负调节剂.
- 这些发现表明,EcTIM-1通过抑制宿主的先天抗病毒免疫力来促进RGNNV感染.
- 这项研究为TIM-1在鱼类抗病毒免疫力中的作用提供了关键的见解,有助于我们了解鱼类疾病抵抗力.
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