肠道病毒71型(Enterovirus type 71,EV71)感染是引起神经系统紊乱、肺水肿、肺出血等严重疾病的主要原因。非结构蛋白2A、3C、3D是EV71在宿主细胞内完成复制和存活的基础,具有不同于肠道病毒其他成员的结构和作用机制。2A和3C蛋白可抑...肠道病毒71型(Enterovirus type 71,EV71)感染是引起神经系统紊乱、肺水肿、肺出血等严重疾病的主要原因。非结构蛋白2A、3C、3D是EV71在宿主细胞内完成复制和存活的基础,具有不同于肠道病毒其他成员的结构和作用机制。2A和3C蛋白可抑制宿主细胞蛋白的表达,从而促进细胞凋亡,3C蛋白还可抑制天然免疫,3D蛋白与病毒的耐高温和高度变异适应性有关。一些小分子物质可在病毒入侵的不同阶段抑制EV71感染。本文就2A、3C、3D蛋白在EV71复制过程中的结构与功能特点以及一些小分子物质在病毒复制中的抑制作用作一综述。展开更多
Enteroviruses(EVs) 3C proteins suppress type I interferon(IFN) responses mediated by retinoid acid-inducible gene I(RIG-I), while an E3 ubiquitin ligase, tripartite motif protein 25(TRIM25)-mediated RIG-I ubiquitinati...Enteroviruses(EVs) 3C proteins suppress type I interferon(IFN) responses mediated by retinoid acid-inducible gene I(RIG-I), while an E3 ubiquitin ligase, tripartite motif protein 25(TRIM25)-mediated RIG-I ubiquitination is essential for RIG-I antiviral activity. Therefore, whether the effect of EVs 3C on RIG-I is associated with TRIM25 expression is worth to be further investigated. Here, we demonstrate that 3C proteins of EV71 and coxsackievirus B3(CVB3) reduced not only RIG-I expression but also TRIM25 expression through protease cleavage activity, while overexpression of TRIM25 restored RIG-I expression and IFN-b production reduced by 3C proteins. Further investigation confirmed that the two amino acids and functional domains in TRIM25 required for RIG-I ubiquitination and TRIM25 structural conformation were essential for the recovery of RIG-I expression. Moreover, we also observed that TRIM25 could rescue RIG-I expression reduced by 3C proteins of CVA6 and EV-D68 but not CVA16. Our findings provide an insightful interpretation of 3C-mediated host innate immune suppression and support TRIM25 as an attractive target against multiple EVs infection.展开更多
文摘肠道病毒71型(Enterovirus type 71,EV71)感染是引起神经系统紊乱、肺水肿、肺出血等严重疾病的主要原因。非结构蛋白2A、3C、3D是EV71在宿主细胞内完成复制和存活的基础,具有不同于肠道病毒其他成员的结构和作用机制。2A和3C蛋白可抑制宿主细胞蛋白的表达,从而促进细胞凋亡,3C蛋白还可抑制天然免疫,3D蛋白与病毒的耐高温和高度变异适应性有关。一些小分子物质可在病毒入侵的不同阶段抑制EV71感染。本文就2A、3C、3D蛋白在EV71复制过程中的结构与功能特点以及一些小分子物质在病毒复制中的抑制作用作一综述。
基金The study was supported by the National Natural Science Foundation of China(No.81672004 and 81930062)the Science and Technology Department of Jilin Province(20190101003JH)the Key Laboratory of Molecular Virology,Jilin Province(20102209)。
文摘Enteroviruses(EVs) 3C proteins suppress type I interferon(IFN) responses mediated by retinoid acid-inducible gene I(RIG-I), while an E3 ubiquitin ligase, tripartite motif protein 25(TRIM25)-mediated RIG-I ubiquitination is essential for RIG-I antiviral activity. Therefore, whether the effect of EVs 3C on RIG-I is associated with TRIM25 expression is worth to be further investigated. Here, we demonstrate that 3C proteins of EV71 and coxsackievirus B3(CVB3) reduced not only RIG-I expression but also TRIM25 expression through protease cleavage activity, while overexpression of TRIM25 restored RIG-I expression and IFN-b production reduced by 3C proteins. Further investigation confirmed that the two amino acids and functional domains in TRIM25 required for RIG-I ubiquitination and TRIM25 structural conformation were essential for the recovery of RIG-I expression. Moreover, we also observed that TRIM25 could rescue RIG-I expression reduced by 3C proteins of CVA6 and EV-D68 but not CVA16. Our findings provide an insightful interpretation of 3C-mediated host innate immune suppression and support TRIM25 as an attractive target against multiple EVs infection.
