Department of Clinical Laboratory, Chongming Brach Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P. R. China.
PLoS One. 2024 Jul 26;19(7):e0307776. doi: 10.1371/journal.pone.0307776. eCollection 2024.
Deubiquitinating enzymes (DUBs) play a pivotal role in regulating the antiviral immune response by targeting members of the RLR signaling pathway. As a pivotal member of the RLR pathway, TRAF3 is essential for activating the MAVS/TBK-1/IRF3 signaling pathway in response to viral infection. Despite its importance, the function of DUBs in the TRAF3-mediated antiviral response is poorly understood. Ubiquitin-specific protease 26 (USP26) regulates the RLR signaling pathway to modulate the antiviral immune response. The results demonstrate that EV71 infection upregulates the expression of USP26. Knockdown of USP26 significantly enhances EV71-induced expression of IFN-β and downstream interferon-stimulated genes (ISGs). Deficiency of USP26 not only inhibits EV71 replication but also weakens the host's resistance to EV71 infection. USP26 physically interacts with TRAF3 and reduces the K63-linked polyubiquitination of TRAF3, thereby promoting pIRF3-mediated antiviral signaling. USP26 physically interacts with TRAF3 and reduces the K63-linked polyubiquitination of TRAF3, thereby promoting pIRF3-mediated antiviral signaling. Conversely, knockdown of USP26 leads to an increase in the K63-linked polyubiquitination of TRAF3. These findings unequivocally establish the essential role of USP26 in RLR signaling and significantly contribute to the understanding of deubiquitination-mediated regulation of innate antiviral responses.
去泛素化酶（DUBs）通过靶向 RLR 信号通路成员在调节抗病毒免疫反应中发挥关键作用。TRAF3 作为 RLR 通路的关键成员，对于病毒感染时激活 MAVS/TBK-1/IRF3 信号通路至关重要。尽管其重要性不言而喻，但 DUBs 在 TRAF3 介导的抗病毒反应中的功能仍知之甚少。泛素特异性蛋白酶 26（USP26）调节 RLR 信号通路以调节抗病毒免疫反应。结果表明，EV71 感染上调 USP26 的表达。USP26 的敲低显著增强了 EV71 诱导的 IFN-β 和下游干扰素刺激基因（ISGs）的表达。USP26 的缺乏不仅抑制 EV71 的复制，而且削弱宿主对 EV71 感染的抵抗力。USP26 与 TRAF3 相互作用，并减少 TRAF3 的 K63 连接多泛素化，从而促进 pIRF3 介导的抗病毒信号。USP26 与 TRAF3 相互作用，并减少 TRAF3 的 K63 连接多泛素化，从而促进 pIRF3 介导的抗病毒信号。相反，USP26 的敲低导致 TRAF3 的 K63 连接多泛素化增加。这些发现明确确立了 USP26 在 RLR 信号中的重要作用，并为理解去泛素化介导的先天抗病毒反应调节做出了重要贡献。
