柯萨奇病毒B组5型非结构蛋白抑制NF-κB信号通路的作用机制研究

Inhibition of NF-κB Signaling Pathway by Non-structural Protein of Coxsackie Virus Group B Type 5

目的 柯萨奇病毒B组5型(CVB5)是手足口病的重要病原体之一,可导致发热、皮疹或疱疹等临床症状,重症者出现神经系统疾病,甚至死亡。天然免疫应答是机体抗病毒入侵的第一道防线,其中核因子κB (NF-κB)是宿主天然免疫反应中的重要蛋白质,然而关于CVB5感染后调控NF-κB介导信号通路的研究尚鲜有报道。方法 本研究通过检测启动子活性、促炎因子水平以及通路中关键蛋白表达等,阐明CVB5对NF-κB信号通路的调控作用机制。结果 CVB5感染可抑制促炎因子表达和p65的磷酸化。CVB5非结构蛋白(NSP)可抑制促炎因子表达以及重要蛋白p65和IκBα的磷酸化。经STRING11.1数据库预测表明,CVB5 3CD蛋白与宿主多聚胞嘧啶结合蛋白1 (PCBP1)具有相互作用,且PCBP1可促进IκBα和p65的磷酸化,抑制病毒复制。结论 CVB5 NSP可负调控NF-κB信号通路,且与3CD相互作用的PCBP1蛋白可通过调控NF-κB通路抑制CVB5复制。本研究探索病毒与宿主天然免疫应答的调控作用,从而为研制抗CVB5感染的药物提供作用靶点。

Objective Coxsackie virus group B type 5(CVB5)is one of the causative agents of hand-foot-mouth disease,which can cause clinical symptoms such as fever,rash or herpes,and neurological complications or even fatalities.The innate immune response is the first line of defense against the viral infection,and the nuclear factor-κB(NF-κB)is a master regulator in the control of immune responses.However,little research has been reported on the regulation of the NF-κB mediated signaling pathway after CVB5 infection.This study explores the regulatory mechanism of virus and the host innate immune response,providing targets for the development of drugs against CVB5 infection.Methods In this study,promoter activity,proinflammatory factor and key proteins expression were detected to investigate the regulatory mechanism of CVB5 on NF-κB signaling.Results CVB5 infection inhibited the expression of proinflammatory factors and the phosphorylated p65 protein expression.Non-structural protein(NSP)of CVB5 inhibited the expression of proinflammatory factor and important proteins,such as the phosphorylated p65 and IκBα.CVB53CD interacted with the host polycytosine binding protein 1(PCBP1)was performed via the STRING 11.1 database,and the PCBP1 inhibited viral replication by promoting the phosphorylation of IκBαand p65.Conclusion These results showed that CVB5 NSP negatively regulated NF-κB signaling pathway,and the PCBP1 protein which interacted with 3CD could inhibit CVB5 replication through activate the NF-κB pathway.