双向调节I型干扰素信号通过血红氧酶-1的双向调节
Miaomiao Wu1,2, Yihui Fan2,3, Lijuan Li1,2,3
1Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
iScience
|February 29, 2024
概括
血红氧酶-1 (HO-1) 通过增强干扰素I (IFN-I) 来促进对病毒感染的免疫反应. 然而,HO-1在氧化应激期间抑制IFN-I信号,揭示了其在细胞防御中的双重作用.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 病毒学 病毒学
背景情况:
- 干扰素-I (IFN-I) 对于免疫反应至关重要,但其失调,通常是由于氧化应激,可能导致病理损伤.
- 血氧酶-1 (HO-1) 是一种由各种压力刺激诱导的关键细胞保护蛋白.
研究的目的:
- 研究HO-1在病毒感染和氧化应激期间调节IFN-I信号传递中的作用.
- 阐明HO-1对IFN-I的双向调节的基础分子机制.
主要方法:
- 使用的SVCV感染模型的春季病毒病.
- 使用HO-1的截断突变来识别功能域.
- 研究了铁离子结合点 (His28) 在HO-1功能中的作用.
- 研究了自途径在HO-1-介导蛋白质降解中的参与.
主要成果:
- 在SVCV感染期间,HO-1促进IFN-I的产生,导致病毒复制减少.
- 完整的HO-1对于其通过IFN-I调解的抗病毒活性至关重要.
- 在过氧化 (H2O2) 诱导的氧化应激下,HO-1 通过自性降解 IRF3/7 来抑制 IFN-I 信号传递.
- 在HO-1的His28铁离子结合部位对IRF3/7降解至关重要.
- 这种调节机制在鱼类和哺乳动物中得到保护.
结论:
- HO-1在调节IFN-I信号传递方面表现出双重作用:它在病毒感染期间增强IFN-I,但在氧化应激下抑制它.
- HO-1通过自来降解IRF3/7的能力是其在氧化应激下对IFN-I的负调节的核心.
- 这些发现揭示了HO-1对IFN-I信号的新型双向调节机制.
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