LRP6通过IFN通路抑制肠道病毒EV71和柯萨奇病毒CA16  

LRP6 Inhibits Enterovirus 71 and Coxsackievirus 16 Through the IFN Pathway

作　　者：郭泽铭 蔡秋虹 GUO Zeming;CAI Qiuhong(Fujian Medical University 2nd Affiliated Hospital,Quanzhou 362000,China;Quanzhou Third Hospital,Quanzhou 362000,China)

机构地区：[1]福建医科大学附属第二医院,泉州362000 [2]泉州市第三医院,泉州362000

出　　处：《病毒学报》2022年第4期858-865,共8页Chinese Journal of Virology

摘　　要：初步探索在EV71和CA16感染过程中,人低密度脂蛋白受体相关蛋白6(Low⁃density lipoprotein receptor⁃related protein 6,LRP6)通过作用于I型干扰素信号通路对EV71和CA16的抑制作用。使用qRT⁃PCR和Western Blot分别检测了EV71和CA16两种病毒感染Vero细胞后LRP6的表达情况;通过TCID50实验检测细胞中EV71和CA16病毒的RNA水平;通过双荧光素酶报告实验检测LRP6对NF⁃κB活化的影响;通过双荧光素酶报告实验检测RIG⁃I转录活性。EV71和CA16感染后,随着感染时间的延长,LRP6的表达逐渐升高;过表达LRP6后,细胞中感染性活病毒滴度也有显著下降;在仙台病毒诱导下,过表达LRP6,NF⁃κB转录活性显著增强;LRP6是通过靶向TBK1及其上游分子来激活I型干扰素通路。LRP6在EV71和CA16感染过程中会增强I型干扰素信号。To preliminarily explore inhibition of human low⁃density lipoprotein receptor⁃related protein 6(LRP6)on enterovirus 71(EV71)and coxsackievirus 16(CA16)by acting on the type⁃I interferon signaling pathway during infections by EV71 and CA16.LRP6 expression in the Vero cell line infected with EV71 and CA16 was detected by real⁃time reverse transcription⁃quantitative polymerase chain reaction and western blotting,respectively.RNA levels of EV71 and CA16 viruses in cells were detected by the median tissue culture infectious dose(TCID50)assay.The effect of LRP6 on nuclear factor⁃kappa B(NF⁃κB)activation was detected by the dual⁃luciferase reporter assay.RIG⁃I transcriptional activity was detected by the dual⁃luciferase reporter assay.After infection by EV71 and CA16,LRP6 expression increased gradually with prolongation of infection time.After LRP6 overexpression,the infectious live virus in cells also decreased significantly.Under induction by the Sendai virus,the transcriptional activity of NF⁃κB was enhanced significantly by LRP6 overexpression.LRP6 activated the type⁃I interferon pathway by targeting TBK1 and its upstream molecules.LRP6 enhances type⁃1 interferon signaling during infection by EV71 and CA16.

关 键 词：低密度脂蛋白受体相关蛋白6 干扰素 肠道病毒71型 柯萨奇病毒16型 

分 类 号：R373.2[医药卫生—病原生物学]