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HCV核心蛋白-ISX轴通过代谢重塑和免疫抑制促进慢性肝病的进展

Li-Ting Wang^1,2, Shen-Nien Wang^3,4,5, Shyh-Shin Chiou^2,6,7

¹Department of Life Science, National Taiwan Normal University, Taipei, 116059, Taiwan.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|June 14, 2023

概括

型肝炎病毒 (HCV) 核心蛋白和肠特异性家庭盒 (ISX) 轴驱动代谢问题和免疫抑制,导致肝纤维化. 针对这一轴为HCV诱导的肝病提供了潜在的治疗策略.

科学领域:

肝病学肝病学是一种肝病学.
病毒学病毒学
免疫学免疫学免疫学

背景情况:

慢性型肝炎病毒 (HCV) 感染带来了重大的公共卫生挑战.
肝脏中HCV诱导的代谢和免疫失调背后的机制仍然不完全理解.

研究的目的:

阐明HCV核心蛋白-肠特异性家庭盒 (ISX) 轴在塑造肝脏病理环境中的作用.
研究这一轴对代谢障碍,免疫抑制和肝纤维化的影响.

主要方法:

使用了转录组分析和转基因小鼠模型.
在体外研究中使用了HCV JFH-1复制物和ISX特定的shRNA.
在HCV感染的HCC患者中进行了临床相关性分析.

主要成果:

发现HCV核心蛋白-ISX轴促进了代谢 (脂质,葡萄糖),纤维基因和免疫调节剂 (金氨酸,PD-L1,B7-2).
在体内,这个轴加剧了代谢功能障碍和免疫抑制,在高脂肪饮食模型中达到肝纤维化.
对ISX和下游调节器的升级与核心蛋白诱导的核因子-κB信号传递有关.
ISX抑制减弱了HCV核心蛋白诱导的代谢和免疫障碍.
从临床上看,HCV核心水平与HCV感染HCC患者的ISX,IDO,PD-L1和B7-2有显著的相关性.

结论:

HCV核心蛋白-ISX轴是驱动慢性HCV感染中代谢失调,免疫抑制和纤维化的关键机制.
这一轴代表了管理HCV引起的肝病的有前途的治疗标.

关键词:

肝炎病毒核心蛋白质是HCV的核心蛋白质.在ISX上,它是ISX.免疫抑制免疫抑制代谢失调是代谢失调的原因之一.编程死亡链条1 (PD-L1) 编程死亡链条1 (PD-L1) 编程死亡链条

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