猪流行性腹泻病毒与宿主抗病毒天然免疫抑制

Inhibitory Mechanism of Host Antiviral Innate Immunity by Porcine Epidemic Diarrhea Virus

猪流行性腹泻病毒(porcine epidemic diarrhea virus,PEDV)能引起猪腹泻等肠道疾病,属于α属冠状病毒,它的爆发给很多国家养猪业造成了严重的经济损失。2010年以来,PEDV感染在中国出现大规模爆发,一种突变型PEDV也于2013年在美国出现并迅速传播。RNA病毒能够通过Toll样受体通路3(TLR3)和RIG-I样受体通路(RLR)诱导I型干扰素的产生。但以往的研究表明,PEDV感染能抑制I型干扰素的合成。近年来有关PEDV调节宿主天然免疫应答的研究取得了很大进展。PEDV主要通过编码作为干扰素拮抗剂的病毒蛋白以及隐藏病毒自身病原相关分子模式(PAMP)等两种方式逃逸宿主天然免疫应答。目前已报道,PEDV非结构蛋白1可通过降解CBP阻碍干扰素调节因子3(IRF-3)组装成增强子复合体;木瓜蛋白酶样蛋白酶可通过其去泛素化酶活性阻断天然免疫信号通路传递;3C样蛋白酶可通过剪切NEMO发挥干扰素拮抗剂活性;核衣壳蛋白通过结合TBK1抑制I型干扰素产生。PEDV也可通过合成加帽酶隐藏其病原相关分子dsRNA来避免激活天然免疫通路。PEDV抗病毒天然免疫机制阐明为研究PEDV感染免疫和致病机制提供了重要的理论依据,为研发抗PEDV新型疫苗和药物提供了基础。

Porcine epidemic diarrhea virus（ PEDV）,a genus-α coronavirus,can cause pig intestinal diseases-porcine epidemic diarrhea（ PED） and has resulted in enormous economic loss in many countries.The large outbreak of PEDV in China has been reported since 2010 and in the United States since 2013.RNA viruses induce the production of type-I interferon（ IFN） through toll-like receptor 3（ TLR3）- and RIG-I-like receptors（ RLR）-dependent pathways. Previous studies have shown that PEDV infection inhibits the synthesis of type-I IFN. Great progress regarding the roles of PEDV in host innate immunity has been made in recent years. PEDV escapes innate immune response by two main ways,one is that PEDV encodes interferon antagonists and the other is that PEDV hides its pathogen-associated molecular patternsdsRNA. At present, PEDV-encoded non-structural protein 1（ nsp1）, papain-like protease,3C-like protease and nucleocapsid protein have been identified as interferon antagonists. The enhanceosome assembly of IRF3 and CREB-binding protein（ CBP） can be interrupted by nsp1 via degrading CBP. TypeI interferon pathway can be negatively regulated by papain-like protease through acting as a viral deubiquitinase. Innate immune signaling pathway can be antagonized by 3C-like protease via cleavingNEMO,and the production of type-I interferon can be inhibited by nucleocapsid protein via binding threonine-protein kinase 1（ TBK1）. PEDV-encoded replicase synthesizes a cap-structure to its dsRNA to avert activating innate immune pathways. These results provide a theoretical basis to investigate the infection,immunity and pathogenicity by PEDV,which may help to develop new vaccines and drugs against PEDV.