猪流行性腹泻病毒逃避宿主干扰素抗病毒作用机制的研究进展

doi:10.16431/j.cnki.1671-7236.2019.07.026

摘要/Abstract

摘要：

猪流行性腹泻病毒（porcine epidemic diarrhea virus，PEDV）是一种全球分布的α冠状病毒，能引起仔猪流行性腹泻，猪流行性腹泻一旦暴发会给养殖业带来巨大的经济损失。在病毒感染期间，Ⅰ型干扰素（type Ⅰ interferon，IFN-Ⅰ）是先天性抗病毒反应的关键介质。大多数冠状病毒通过限制IFN的产生和IFN应答的激活而产生一些策略以规避IFN应答。然而，PEDV颉颃IFN抗病毒作用的分子机制尚未完全清楚。猪感染PEDV后，机体的先天免疫不能有效抵抗PEDV的侵害，PEDV通过限制或阻断IFN的功能和隐藏自身的病原体相关分子模式（pathogen-associated molecular patterns，PAMP）两种途径逃逸宿主先天免疫。在此过程中，PEDV的结构蛋白和非结构蛋白及一些蛋白酶起到了关键作用，核衣壳（nucleocapsid，N）蛋白能抑制IFN-Ⅰ的产生，协助病毒逃避机体的抗病毒天然免疫，木瓜样蛋白酶通过去泛素化酶活性阻断天然免疫信号通路，PEDV也可通过阻断双链核糖核酸（double-stranded RNA，dsRNA）诱导IFN-Ⅰ的产生，以逃避宿主的先天免疫。这些研究为深入了解IFN在PEDV致病过程中的作用及PEDV逃避IFN抗病毒的机制提供了理论依据，并有助于深入了解病毒与宿主先天性免疫之间的关系，同时也为PEDV的防治及PEDV疫苗的研发提供参考。

关键词: 猪流行性腹泻; 逃避; 干扰素(IFN); 先天免疫

Abstract:

Porcine epidemic diarrhea virus (PEDV) is a globally distributed alpha coronavirus,which can cause epidemic diarrhea in piglets.Porcine epidemic diarrhea outbreak will bring huge economic losses to the breeding industry.Type Ⅰ interferon (IFN-Ⅰ) is a key mediator of innate antiviral responses during viral infection.Most coronaviruses produce strategies to limit IFN response by limiting IFN production and activation of IFN responses.However,the molecular mechanism by which PEDV antagonizes the antiviral effect of IFN is not fully understood.After the pig is infected with PEDV,the body's innate immunity is not effective against PEDV.PEDV escapes host innate immunity by limiting or blocking the function of IFN and hiding its pathogen-associated molecular patterns (PAMP).In this process,structural and non-structural proteins of PEDV and some proteases play a key role.The nucleocapsid (N) protein can inhibit the production of IFN-Ⅰ and help the virus escape the antiviral natural immunity of the body.Papain-like protease blocks the natural immune signaling pathway by deubiquitinating enzyme activity.PEDV also evades host innate immunity by blocking the production of IFN-Ⅰ induced by double-stranded RNA (dsRNA).These studies provide a theoretical basis for understanding the role of IFN in the pathogenesis of PEDV and the mechanism by which PEDV escapes IFN against viruses,and help to understand the relationship between the virus and the host's innate immunity,it also provides a theoretical basis for the prevention and treatment of PEDV and the development of PEDV vaccine.

Key words: porcine epidemic diarrhea; escape; interferon (IFN); innate immune

中图分类号:

S852.651

朱红晓, 王秋霞, 李鹏, 欧长波, 胡会龙, 魏小兵, 张秀林, 刘兴友. 猪流行性腹泻病毒逃避宿主干扰素抗病毒作用机制的研究进展[J]. 《中国畜牧兽医》, 2019, 46(7): 2096-2102.

ZHU Hongxiao, WANG Qiuxia, LI Peng, OU Changbo, HU Huilong, WEI Xiaobing, ZHANG Xiulin, LIU Xingyou. Research Progress on Mechanism of Porcine Epidemic Diarrhea Virus Evading the Antiviral Effect of Host Interferon[J]. , 2019, 46(7): 2096-2102.

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