2023年6月，中国天津大学生命科学学院;天津市生物大分子结构功能与应用重点实验室研究所;天津大学环境科学与工程学院(School of Life Sciences, Tianjin University, Tianjin, China；Institute of Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin, China；School of Environmental Science and Engineering, Tianjin University, Tianjin, China) Jun Kang老师研究团队在《MICROBIOL SPECTR》上发表论文：

“Enterovirus D68 VP3 Targets the Interferon Regulatory Factor 7 To Inhibit Type I Interferon Response”

“肠病毒D68 VP3靶向干扰素调节因子7抑制I型干扰素应答”

Abstract：

Enterovirus D68 (EV-D68) is a globally emerging pathogen causing severe respiratory illnesses mainly in children. The protease from EV-D68 could impair type I interferon (IFN-I) production. However, the role of the EV-D68 structural protein in antagonizing host antiviral responses remains largely unknown. We showed that the EV-D68 structural protein VP3 interacted with IFN regulatory factor 7 (IRF7), and this interaction suppressed the phosphorylation and nuclear translocation of IRF7 and then repressed the transcription of IFN. Furthermore, VP3 inhibited the TNF receptor associated factor 6 (TRAF6)-induced ubiquitination of IRF7 by competitive interaction with IRF7. IRF7Δ305-503 showed much weaker interaction ability to VP3, and VP3Δ41-50 performed weaker interaction ability with IRF7. The VP3 from enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) was also found to interact with the IRF7 protein. These results indicate that the enterovirus structural protein VP3 plays a pivotal role in subverting host innate immune responses and may be a potential target for antiviral drug research. IMPORTANCE EV-D68 is a globally emerging pathogen that causes severe respiratory illnesses. Here, we report that EV-D68 inhibits innate immune responses by targeting IRF7. Further investigations revealed that the structural protein VP3 inhibited the TRAF6-induced ubiquitination of IRF7 by competitive interaction with IRF7. These results indicate that the control of IRF7 by VP3 may be a mechanism by which EV-D68 represses IFN-I production.

摘要：

肠病毒D68 (EV-D68)是一种全球新发病原体，主要在儿童中引起严重呼吸道疾病。EV-D68的蛋白酶可以抑制I型干扰素(IFN-I)的产生。然而，EV-D68结构蛋白在拮抗宿主抗病毒反应中的作用在很大程度上仍然未知。研究人员发现EV-D68结构蛋白VP3与IFN调控因子7 (IRF7)相互作用，抑制IRF7的磷酸化和核易位，进而抑制IFN的转录。此外，VP3通过与IRF7的竞争性相互作用抑制TNF受体相关因子6 (TRAF6)诱导的IRF7泛素化。IRF7Δ305-503与VP3的互作能力弱得多，VP3Δ41-50与IRF7的互作能力弱得多。来自肠病毒A71 (EV-A71)和柯萨奇病毒A16 (CV-A16)的VP3也被发现与IRF7蛋白相互作用。这些结果表明，肠道病毒结构蛋白VP3在破坏宿主先天免疫应答中起着关键作用，可能是抗病毒的药物研究的潜在靶点。EV-D68是一种全球新发病原体，可引起严重呼吸道疾病。在这里，研究人员报道EV-D68通过靶向IRF7抑制先天免疫反应。进一步研究发现，结构蛋白VP3通过与IRF7的竞争相互作用抑制traf6诱导的IRF7泛素化。这些结果表明VP3对IRF7的控制可能是EV-D68抑制IFN-I产生的机制之一。

该论文中，对HEK293T、横纹肌肉瘤(RD)和HeLa细胞及其经过脂质体转染细胞的体外培养是使用Ausbian特级胎牛血清完成的。