EBV对宿主免疫的调控作用研究进展

doi:10.19586/j.2095-2341.2023.0048

生物技术进展 ›› 2023, Vol. 13 ›› Issue (5): 681-689.DOI: 10.19586/j.2095-2341.2023.0048

EBV对宿主免疫的调控作用研究进展

张旭娟(), 赵鹏翔(), 刘子怡, 蔡子松, 刘梦昱, 谢飞, 马雪梅

北京工业大学环境与生命学部，北京 100124

收稿日期:2023-04-12 接受日期:2023-07-10 出版日期:2023-09-25 发布日期:2023-10-10
通讯作者: 赵鹏翔
作者简介:张旭娟E-mail: 1094191300@qq.com；
基金资助:
国家自然科学基金项目(81602408);北京市科技新星计划项目(20220484218)

Research Progress on the Immune Regulation of EBV on the Host

Xujuan ZHANG(), Pengxiang ZHAO(), Ziyi LIU, Zisong CAI, Mengyu LIU, Fei XIE, Xuemei MA

Faculty of Environment and Life，Beijing University of Technology，Beijing 100124，China

Received:2023-04-12 Accepted:2023-07-10 Online:2023-09-25 Published:2023-10-10
Contact: Pengxiang ZHAO

摘要/Abstract

摘要：

EB病毒（epstein-barr virus，EBV）在人群中的感染率高达90%，其能够通过对宿主的免疫调控作用在人体内建立长期感染。众多肿瘤的发生及发展与EBV对宿主免疫的调控密切相关，但目前关于EBV的免疫调控作用机制尚未完全阐明。EBV在不同的感染状态下均发展出了一系列对宿主的免疫调控策略，即主要通过靶向Toll样受体(Toll like receptors， TLRs)信号通路，利用或限制部分免疫效应以促进长期感染的建立和逃避宿主免疫监控，从而维持EBV基因组的稳定存在。概述了EBV在潜伏期和裂解期与宿主之间的相互作用，探讨了EBV逃避宿主免疫的策略，旨在为病毒感染防治和病毒相关肿瘤的治疗提供基础理论依据及研究思路。

关键词: EB病毒, Toll样受体, 免疫调控, 核因子κB

Abstract:

As a virus with a human infection rate of up to 90%， EBV can establish long-term infection in the human body through the immune regulation of the host. The occurrence and development of many tumors are closely related to the regulation of host immunity by EBV， but the mechanism of immune regulation by EBV has not been fully elucidated. EBV has developed a series of strategies for host immune regulation in different infection states， mainly by targeting Toll like receptors（TLRs） signaling pathways， using or limiting part of their immune effects to promote the establishment of long-term infection and evade host immune surveillance to maintain the stability of the EBV genome. This article reviewed the immunoregulatory mechanism of EBV， a double-stranded DNA herpesvirus， in order to provide basic theoretical basis and research ideas for the prevention and treatment of virus infection and virus-associated tumors.

Key words: epstein-barr virus, Toll like receptors, immune regulation, NF-κB

中图分类号:

Q939.91

张旭娟, 赵鹏翔, 刘子怡, 蔡子松, 刘梦昱, 谢飞, 马雪梅. EBV对宿主免疫的调控作用研究进展[J]. 生物技术进展, 2023, 13(5): 681-689.

Xujuan ZHANG, Pengxiang ZHAO, Ziyi LIU, Zisong CAI, Mengyu LIU, Fei XIE, Xuemei MA. Research Progress on the Immune Regulation of EBV on the Host[J]. Current Biotechnology, 2023, 13(5): 681-689.

图/表 4

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潜伏类型	EBV基因	EBV蛋白	肿瘤
潜伏0期	EBERs、BARTs	无	无
潜伏Ⅰ期	EBERs、BARTs、EBNA1	EBNA1	Burkitt's淋巴瘤、胃癌
潜伏Ⅱ期	EBERs、BARTs、EBNA1、LMP1/2	EBNA1、LMP1/2	鼻咽癌、霍奇金瘤、NK/T淋巴瘤
潜伏Ⅲ期	所有潜伏基因	EBNA1-6、LMP1/2	移植后淋巴瘤

潜伏类型	EBV基因	EBV蛋白	肿瘤
潜伏0期	EBERs、BARTs	无	无
潜伏Ⅰ期	EBERs、BARTs、EBNA1	EBNA1	Burkitt's淋巴瘤、胃癌
潜伏Ⅱ期	EBERs、BARTs、EBNA1、LMP1/2	EBNA1、LMP1/2	鼻咽癌、霍奇金瘤、NK/T淋巴瘤
潜伏Ⅲ期	所有潜伏基因	EBNA1-6、LMP1/2	移植后淋巴瘤

基因产物	功能
LMP1	模拟CD40介导B细胞转化和存活^[26] 激活NF-κB和JAK/STAT通路以及干扰素刺激基因ISGs^[27] 招募并诱导IRF7表达^[28] 减少TLR9的表达^[29] 抑制EBV裂解复制^[27]
LMP2a	抑制NF-κB、IL-6和JAK/STAT通路(上皮肿瘤细胞)^[30] 模拟BCR诱导NF-κB和PI3K/AKT通路(B细胞)^[31] 减少上皮细胞对IFNα和IFNβ的反应性^[32] 促进B细胞存活^{[31, 33]}
LMP2b	减少上皮细胞对IFNα和IFNβ的反应性^[32]
EBNA1	抑制经典NF-κB通路^[34] 降低NK细胞对EBV感染的识别^[35]
EBNA2	诱导LMP1/2表达^[36] 诱导低水平的IFNβ^[37] 选择性抑制ISGs的产生^[38] 上调IL-18受体的表达^[39] 加强STATA3的活性^[40]
EBERs	抑制PKR活性^[41] 抑制IFNα诱导的凋亡^[41] 诱导依赖于TLR3的炎症反应^[42]
BARTs	下调NLRP3^[43] 下调IFNγ转录因子^[41] 抑制STAT1表达^[44]

基因产物	功能
LMP1	模拟CD40介导B细胞转化和存活^[26] 激活NF-κB和JAK/STAT通路以及干扰素刺激基因ISGs^[27] 招募并诱导IRF7表达^[28] 减少TLR9的表达^[29] 抑制EBV裂解复制^[27]
LMP2a	抑制NF-κB、IL-6和JAK/STAT通路(上皮肿瘤细胞)^[30] 模拟BCR诱导NF-κB和PI3K/AKT通路(B细胞)^[31] 减少上皮细胞对IFNα和IFNβ的反应性^[32] 促进B细胞存活^{[31, 33]}
LMP2b	减少上皮细胞对IFNα和IFNβ的反应性^[32]
EBNA1	抑制经典NF-κB通路^[34] 降低NK细胞对EBV感染的识别^[35]
EBNA2	诱导LMP1/2表达^[36] 诱导低水平的IFNβ^[37] 选择性抑制ISGs的产生^[38] 上调IL-18受体的表达^[39] 加强STATA3的活性^[40]
EBERs	抑制PKR活性^[41] 抑制IFNα诱导的凋亡^[41] 诱导依赖于TLR3的炎症反应^[42]
BARTs	下调NLRP3^[43] 下调IFNγ转录因子^[41] 抑制STAT1表达^[44]

裂解类型	基因产物	功能
立即早期基因	BZLF1	抑制TNFα和IFNγ受体的表达^[55] 抑制IRF7、IFNα和IFNβ的表达^[57] 调节NF-κB活性^[58-59] 调节TNFα、p53信号^[67] 促进ATF-2的活化^[68] 抑制MHC-1表面蛋白的表达^[69-70] 促进PML小体扩散^[71]
立即早期基因	BRLF1	抑制IRF3/7的表达^[57] 抑制IFNβ的产生^[55]
早期基因	BGLF4	抑制IRF3的磷酸化^[60] 减少IFNβ的产生^[61] 抑制NF-κB活性^[62]
	BGLF5	下调TLR2和TLR9^[72] 降低HLA I和HLA II的表达^[73]
	dUTPase	诱导NF-κB激活^[65] 诱导炎症因子的产生^[66]
晚期基因	BPLF1	干扰NF-κB激活^[74]
晚期基因	LF2	抑制IFNα^[63]

EBV对宿主免疫的调控作用研究进展

Research Progress on the Immune Regulation of EBV on the Host

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