日本脑炎病毒免疫逃逸分子机制研究进展

doi:10.11843/j.issn.0366-6964.2024.06.009

摘要/Abstract

摘要：

日本脑炎(Japanese encephalitis，JE)是由日本脑炎病毒(Japanese encephalitis virus，JEV)引起的一种蚊媒性人兽共患传染病，虽然已有商品化疫苗，但疫苗的预防具有一定的局限性且至今尚无有效药物治疗，一旦暴发将威胁人们的生命健康和公共安全，造成重大经济损失。JEV含有数量众多具有免疫逃逸功能的编码蛋白，这些蛋白逃逸宿主免疫功能的机制多样且复杂，但其机制仍不完全清楚。同时，JEV复杂的免疫逃逸机制可能是阻碍疫苗免疫保护效果的关键因素。因此，本文主要对JEV通过抑制干扰素反应，调节细胞凋亡、焦亡、自噬及宿主miRNA等多种途径逃逸机体先天免疫和适应性免疫机制进行概述，以期为JEV致病机理的研究和疫苗研发提供思路与理论基础。

关键词: 日本脑炎病毒, 免疫逃逸, 天然免疫, 适应性免疫

Abstract:

Japanese encephalitis (JE) is a mosquito-borne animal disease caused by Japanese encephalitis virus (JEV), although commercially vaccines are availabe, however, the vaccines has certain limitations and there is no effective drug treatment so far, and once the outbreak occurs, people's life and health as well as the public safety will be threatened, thus resulting in significant economic losses. JEV contains a large number of encoded proteins with immune escape function. The mechanism of these proteins escaping host immune function is diverse and complex, and the mechanism of which still remains unclear. At the same time, the complex immune escape mechanism of JEV may be the key factor hindering the immune protection effect of vaccine. Therefore, this paper mainly summarizes the mechanism of JEV escaping innate and adaptive immunity by inhibiting interferon response, regulating apoptosis, pyroptosis, autophagy and host miRNA to provide ideas and theoretical basis for the research of JEV pathogenesis and vaccine development.

Key words: Japanese encephalitis virus, immune escape, innate immunity, adaptive immunity

中图分类号:

S852.65

何松, 汤德元, 曾智勇, 王彬, 黄涛, 毛茵茗, 周飘, 廖正波, 陈旭, 袁盛林, 胡雯雯, 周敏. 日本脑炎病毒免疫逃逸分子机制研究进展[J]. 畜牧兽医学报, 2024, 55(6): 2368-2378.

Song HE, Deyuan TANG, Zhiyong ZENG, Bin WANG, Tao HUANG, Yinming MAO, Piao ZHOU, Zhengbo LIAO, Xu CHEN, Shenglin YUAN, Wenwen HU, Min ZHOU. Research Progress on the Molecular Mechanisms of Immune Escape of Japanese Encephalitis Virus[J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(6): 2368-2378.

图/表 1

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JEV免疫逃逸途径 Immune escape pathway of JEV	作用方式 Mode of action	功能 Function	参考文献 References
细胞凋亡 Apoptosis	上调CHOP	诱导细胞凋亡，促进自身扩散	[22]
	与GRP78、PHB、hnRNPC 3种蛋白结合	引起ERS相应蛋白的表达失调，诱导细胞凋亡	[23]
	NS4B蛋白与PERK结合	触发PERK/eIF2-α/ATF4/CHOP凋亡途径，在体内外诱导神经元凋亡	[24]
	下调STAT3，降低Foxo表达	下调抗凋亡蛋白表达	[25]
坏死性凋亡和细胞焦亡 Necrotic apoptosis and pyroptosis	上调炎症因子TNF-α表达	介导MLKL诱导细胞坏死性凋亡	[35-36]
坏死性凋亡和细胞焦亡 Necrotic apoptosis and pyroptosis	NS2B-3蛋白与AXL结合	抑制PI3K/Akt信号通路，增加细胞坏死性凋亡和焦亡	[37]
细胞自噬 Autophagy	上调LC3	诱导细胞自噬	[41]
	上调PARP1	负向调节Akt，促进细胞自噬	[42]
	ERS途径	促进细胞自噬	[43]
miRNA	上调miR-29b、miR-19b-3p、miR-15b和miR-155表达	增强NF-κB活性，促进炎症因子的产生	[48-52]
miRNA	上调miR-301a表达	抑制IRF1和SOCS5的表达，阻断Ⅰ型IFN反应	[54]
抑制IFN反应 Inhibition of interferon response	NS5阻断JAK/STAT、抑制IRF3和NF-κB核转位	抑制Ⅰ型IFN	[59-60]
	NS1′蛋白增强CDK1磷酸化	抑制MAVS介导的IFN-β表达	[63-64]
	NS4B靶向TLR3和TRIF	抑制IRF3磷酸化和IFN-β的产生	[67]

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