a 武汉大学生命科学学院、病毒学国家重点实验室
b 武汉大学医学研究院
肠道病毒71型(EV71)为主的手足口病疫情在亚太地区多次暴发,对婴幼儿健康构成严重威胁。因此,对肠道病毒的感染机制和致病性的研究变得越来越重要。3D聚合酶是EV71复制过程中最关键的RNA依赖RNA聚合酶(RdRp),被广泛用作抑制EV71感染的靶点。在这项研究中,我们报道了一种新的宿主蛋白AIMP2,它可以结合3D聚合酶并抑制EV71复制。进一步研究表明,AIMP2募集E3连接酶SMURF2,介导3D聚合酶的多泛素化和降解。此外,AIMP2的抗病毒作用也适用于CVA16和CVB1血清型。在这项工作中,我们旨在研究AIMP2在EV71感染过程中的动态调控功能,揭示一种新的抗病毒机制,并为开发抗肠道病毒治疗策略提供新的见解。
Fig. 1. AIMP2 mRNA and protein levels were downregulated during EV71 infection.
Fig. 2. Overexpression of AIMP2 inhibits EV71 infection.
Fig. 3. Knockdown of AIMP2 promotes EV71 infection.
Fig. 4. AIMP2 affects the replication of EV71, does not affect the attachment, entry and translation of EV71.
Fig. 5. AIMP2 interacts with EV71 3D polymerase.
Fig. 6. AIMP2 degrades 3D polymerase through the ubiquitin-proteasome pathway.
Fig. 7. AIMP2 recruits the E3 ligase SMURF2 to promote the degradation of 3D polymerase.
Fig. S1. AIMP2 inhibits the infection of enterovirus serotypes CVA16 and CVB1.
Fig. S2 The EV71 3C protease downregulates AIMP2.
Fig. S3 AIMP2 does not interact with EV71 helicase 2C.
相关阅读:
m5C甲基转移酶NSUN2调控EV71复制的机制研究 NSUN2 mediates distinct pathways to regulate enterovirus 71 replication 将HiBiT整合到肠道病毒中:推进肠道病毒学研究的通用工具 Integration of HiBiT into enteroviruses: A universal tool for advancing enterovirus virology research 防己诺林碱可作为广谱的抗肠道病毒抑制剂 Identification of fangchinoline as a broad-spectrum enterovirus inhibitor through reporter virus based high-content screening RAF抑制剂PLX8394通过阻断RAF/MEK/ERK信号通路抑制EV71的复制
PLX8394, a RAF inhibitor, inhibits enterovirus 71 replication by blocking RAF/MEK/ERK signaling