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ARRDC4介导的糖解通过果糖-1,6-双增强了对流感A病毒的先天免疫力

Yuhan Li^1,2,3,4, Zhen Wang^1,2,3, Jie Wang^1,2,3

¹State Key Laboratory of Veterinary Public Health and Safety, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China.

Proceedings of the National Academy of Sciences of the United States of America

|August 28, 2025

概括

含有4 (ARRDC4) 的阿雷斯域通过葡萄糖代谢酶果酶,肌肉类型 (PFKM) 和其产物果糖-1,6-双酸盐 (FBP) 增强抗病毒免疫力. 这种途径增强了对病毒感染的先天免疫反应.

科学领域:

免疫代谢
病毒学
分子生物学

背景情况:

葡萄糖代谢在病毒感染期间显著影响先天免疫反应.
关联葡萄糖代谢与抗病毒免疫的特定酶,天然产品和调节机制尚不完全理解.
含有4的阿雷斯域 (ARRDC4) 被认为是葡萄糖代谢的关键调节剂.

研究的目的:

阐明ARRDC4在感知病毒感染和调节先天免疫反应中的作用.
确定涉及ARRDC4介导抗病毒免疫的特定代谢途径和分子.
研究针对病毒感染的免疫代谢途径的潜在治疗策略.

主要方法:

研究了ARRDC4和流感A病毒 (IAV) PA蛋白之间的相互作用.
评估ARRDC4对果酸酶,肌肉类型 (PFKM) 活性和果糖-1,6-双酸盐 (FBP) 生产的影响.
分析了FBP对HSP90β泛化,IKKβ/IKKε相互作用和NF-κB/IRF7激活的影响.
在体外和体内评估FBP补充剂的抗病毒作用.

主要成果:

ARRDC4与病毒PA蛋白相互作用,检测出IV感染.
调节后的ARRDC4可增强PFKM活动,增加FBP的产量.
FBP抑制HSP90β的降解,促进与IKKβ/ IKKε的相互作用,从而增强NF-κB和IRF7介导的免疫力.
FBP补充剂显著增强了IFN-β介导的抗病毒本质免疫力.

结论:

发现了一种新的免疫代谢调节机制,
PFKM-FBP代谢轴对于调节抗病毒天生的免疫力至关重要.
与FBP相关的代谢是治疗病毒感染的潜在治疗点.

关键词:

在ARRDC 果糖-1,6-双酸盐流感的天生的免疫力病毒复制

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