猪流行性腹泻病毒蛋白与宿主蛋白相互作用的研究进展

doi:10.11843/j.issn.0366-6964.2025.06.007

摘要/Abstract

摘要：

猪流行性腹泻(porcine epidemic diarrhea，PED)是由猪流行性腹泻病毒(porcine epidemic diarrhea virus，PEDV)引起的高度接触性传染病，主要症状为呕吐、水样腹泻、脱水和体重下降，哺乳仔猪感染后死亡率可高达100%，给全球养猪业带来了巨大的经济损失。目前尚无有效的治疗药物，且其疫苗也存在一定的局限性。在病毒感染过程中，病毒蛋白与宿主蛋白通过相互作用，一方面促进病毒逃避宿主先天免疫以完成其复制，另一方面调节宿主免疫反应以抑制病毒感染。因此，鉴定病毒蛋白与宿主蛋白相互作用对于了解宿主对病毒感染的防御和病毒性传染病的发病机制至关重要，从而发现新的抗病毒靶点。本文详细阐述了PEDV感染过程中的病毒蛋白与宿主蛋白的相互作用，总结了PEDV的致病机制，以期为设计有效的疫苗或药物来预防和控制PEDV的传播提供新思路。

关键词: 猪流行性腹泻病毒, 病毒蛋白, 宿主蛋白, 蛋白相互作用

Abstract:

Porcine epidemic diarrhea (PED) is a highly contagious disease caused by the porcine epidemic diarrhea virus (PEDV), characterized by symptoms such as vomiting, watery diarrhea, dehydration and weight loss. The mortality rate of suckling piglets after infection can be as high as 100%, resulting in significant economic losses to the global pig industry. Currently, there are no effective therapeutic drugs available for PEDV, and vaccines have certain limitations. During viral infection, viral proteins interact with host proteins to evade host innate immunity while promoting replication on one hand and regulating the host immune response to inhibit viral infection on the other hand. Therefore, identifying viral proteins that interact with host proteins is crucial for understanding host defense against viral infections and pathogenesis of infectious diseases leading to novel antiviral targets discovery. This review elaborates on protein interactions between viruses and hosts during PEDV infections while summarizing its pathogenic mechanism to provide new ideas for designing effective vaccines or drugs aimed at preventing and controlling PEDV spread.

Key words: porcine epidemic diarrhea virus, viral proteins, host proteins, protein-protein interaction

中图分类号:

S852.659.6

周敏, 汤德元, 曾智勇, 王彬, 黄涛, 胡雯雯, 毛茵茗, 周飘, 何松. 猪流行性腹泻病毒蛋白与宿主蛋白相互作用的研究进展[J]. 畜牧兽医学报, 2025, 56(6): 2600-2612.

ZHOU Min, TANG Deyuan, ZENG Zhiyong, WANG Bin, HUANG Tao, HU Wenwen, MAO Yinming, ZHOU Piao, HE Song. Research Progress on the Interaction between Porcine Epidemic Diarrhea Virus Proteins and Host Proteins[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(6): 2600-2612.

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分类 Classification	PEDV蛋白 PEDV proteins	宿主蛋白 Host proteins	生物学作用 The biological roles	参考文献 References
结构蛋白 Structural proteins	S	pAPN、SA、HS、DC-SIGN、 L-SIGN	介导病毒的附着和内化	[9]
		DNAJA3	抑制PEDV的增殖	[10]
		HSPA5	通过内体/溶酶体途径参与PEDV的运输，促进其附着和内化	[11]
	E	IRF3	抑制RIG-Ⅰ介导的IFN-β和ISGs的产生	[14]
		KPNA2	降解E蛋白，抑制PEDV的复制	[15]
	M	eIF3L、CDC42、Rab11A	eIF3L负调控PEDV复制	[20]
		IRF7	抑制TBK1/IKKε诱导的IRF7磷酸化和二聚化，下调IFN-Ⅰ的表达	[21]
		HSP70	利于PEDV蛋白表达和后代病毒粒子的产生	[23]
		S100A11、PPID	两种蛋白抑制PEDV复制	[24]
	N	TBK1	阻断IRF3的磷酸化和核易位，从而抑制IRF3介导的IFN-Ⅰ的产生	[27]
		NPM1	提高宿主细胞存活率以促进PEDV增殖	[28]
		P53	抑制cyclin A的表达水平，导致细胞周期阻滞在S期	[30]
		PABPC1	在转录和翻译水平上抑制PEDV的复制	[31]
		TRIM21	以蛋白酶体依赖方式靶向N蛋白的降解	[32]
		IRAV、RALY、PRPF19	募集E3泛素连接酶MARCH8促进N蛋白的泛素化和降解	[33-35]
		hnRNPK、PTBP1、FUBP3、TARDBP	通过MARCH8-NDP52-自噬体途径降解N蛋白，并诱导IFN-Ⅰ的产生	[36-39]
辅助蛋白 accessory protein	ORF3	PDI	触发内质网应激反应，并诱导自噬	[43]
辅助蛋白 accessory protein		VPS36	降解ORF3进而抑制PEDV的复制	[44]

PEDV非结构蛋白 PEDV nonstructural proteins	宿主蛋白 Host proteins	生物学作用 The biological roles	参考文献 References
Nsp2	FBXW7	降解FBXW7从而拮抗宿主的抗病毒反应	[48]
Nsp3	RIG-Ⅰ、STING	促进其去泛素化，以拮抗其介导的IFN-β的产生	[81]
Nsp5	NEMO	在NEMO Q23处将其切割，以抑制RIG-Ⅰ/MDA5通路的激活，IFN-β的产生	[50]
	pGSDMD	在pGSDMD Q193-G194处将其裂解，从而抑制焦亡	[53]
Nsp6	GRAMD4	降解GRAMD4，拮抗GRAMD4加剧的细胞凋亡	[56]
Nsp7	MDA5	使MDA5失活，阻断MDA5介导的IFN-β产生	[60]
	STAT1、STAT2	抑制JAK-STAT介导的IFN信号转导和ISGs的产生	[61]
Nsp9	HNRNPA3	增强SREBF1的转录活性, 从而增加细胞脂质积累，促进PEDV复制	[64]
	HIST2H2BE	抑制内质网应激介导的细胞凋亡从而有利于病毒增殖	[65]
Nsp12	RNF7	RNF7负调控PEDV复制	[67]
Nsp13	HNRNPU	降低IRF3的磷酸化和下游ISGs的表达，以抑制宿主抗病毒反应	[70]
	DNMT3b	引起FcRn启动子的异常甲基化从而抑制FcRn的转录和翻译	[72]
Nsp14	IKKα、IKKβ、p65	抑制NF-κB通路激活以及促炎细胞因子的早期产生	[75]
Nsp15	MAVS	依赖于蛋白酶体系统降解MAVS，从而拮抗宿主抗病毒反应	[79]

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