Huang Mengmeng, Xu Mengmeng, Han Jingzhe, Ke Erjing, Niu Xinxin, Zhang Yulong, Wang Guodong, Yu Hangbo, Liu Runhang, Wang Suyan, Liu Yongzhen, Chen Yuntong, Han Jinze, Wu Ziwen, Cui Hongyu, Zhang Yanping, Duan Yulu, Gao Yulong, Qi Xiaole
Avian Immunosuppressive Diseases Division, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, China.
World Organization for Animal Health (WOAH) Reference Laboratory for Infectious Bursal Disease, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin, China.
PLoS Pathog. 2025 Mar 11;21(3):e1012985. doi: 10.1371/journal.ppat.1012985. eCollection 2025 Mar.
The inflammatory response is an essential component of innate immunity to defense against pathogens. Infectious bursal disease (IBD) is the most important immunosuppressive disease in chickens and is caused by the infectious bursal disease virus (IBDV). Acute inflammation is a typical pathogenic process for IBD, however, the underlying mechanism is not clear. Here, we report that IBDV induces obvious inflammatory response in vivo and in vitro. Furthermore, viral VP2 is identified as an important inflammatory stimulus. It is observed that IBDV VP2 can activate NF-κB signaling pathway and then increase IL-1β production. In detail, IBDV VP2 interacts with myeloid differentiation primary response gene 88 (MyD88), potentiates the oligomerization of MyD88 and assembly of MyD88 complex, which is one important element leading to NF-κB signaling pathway activation and IL-1β production increase. More meaningfully, residues 253/284 of viral VP2 are significantly involved in IBDV-induced inflammatory response through modulating the interaction strength between VP2 and MyD88 and the following MyD88-NF-κB-IL-1β signaling pathway. This study reveals one molecular mechanism that trigger inflammation during IBDV infection, which is of great significance for a deeper understanding of the pathogenic mechanisms of IBDV.
炎症反应是机体抵御病原体的固有免疫的重要组成部分。传染性法氏囊病（IBD）是鸡最重要的免疫抑制性疾病，由传染性法氏囊病病毒（IBDV）引起。急性炎症是IBD的典型致病过程，但其潜在机制尚不清楚。在此，我们报道IBDV在体内和体外均可诱导明显的炎症反应。此外，病毒VP2被确定为一种重要的炎症刺激物。研究发现IBDV VP2可激活NF-κB信号通路，进而增加IL-1β的产生。具体而言，IBDV VP2与髓样分化初级反应基因88（MyD88）相互作用，增强MyD88的寡聚化及MyD88复合物的组装，这是导致NF-κB信号通路激活和IL-1β产生增加的一个重要因素。更有意义的是，病毒VP2的253/284位残基通过调节VP2与MyD88之间的相互作用强度以及随后的MyD88-NF-κB-IL-1β信号通路，显著参与IBDV诱导的炎症反应。本研究揭示了IBDV感染过程中引发炎症的一种分子机制，这对于深入了解IBDV的致病机制具有重要意义。
