PDF(Pubmed)
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：
肠道病毒D68（EV-D68）是一种全球新兴的病原体，主要在儿童中引起严重的呼吸道疾病。来自EV-D68的蛋白酶可损害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仍不清楚.我们发现EV-D68结构蛋白VP3与IFN调节因子7（IRF7）相互作用，这种相互作用抑制了IRF7的磷酸化和核易位，然后抑制了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的相互作用能力较弱，而VP3Δ41-50与IRF7的相互作用能力较弱。还发现来自肠道病毒A71(EV-A71)和柯萨奇病毒A16(CV-A16)的VP3与IRF7蛋白相互作用。这些结果表明，肠道病毒结构蛋白VP3在颠覆宿主先天免疫反应中起着关键作用，可能是抗病毒药物研究的潜在靶标。重要性EV-D68是一种全球新兴的病原体，可导致严重的呼吸道疾病。这里,我们报道EV-D68通过靶向IRF7抑制先天免疫应答.进一步的研究表明，结构蛋白VP3通过与IRF7的竞争性相互作用抑制了TRAF6诱导的IRF7的泛素化。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。
