Key Laboratory of Bio-Resources and Eco-Environment, Ministry of Education, Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province, College of Life Science, Sichuan University, Chengdu, 610064, China.
Vet Res. 2024 Nov 5;55(1):141. doi: 10.1186/s13567-024-01396-6.
Infectious bronchitis virus (IBV) is the causative agent of infectious bronchitis (IB), a severe disease that primarily affects young chickens and poses a significant challenge to the global poultry industry. Understanding the complex interaction between the virus and its host is vital for developing innovative antiviral strategies. Long non-coding RNA (lncRNA) plays a crucial role in regulating host antiviral immune responses. Our previous studies have shown that IBV infection disrupts the stability of lncRNA in host cells, indicating a potential regulatory role for lncRNA in IBV pathogenesis. It is still not clear how lncRNA precisely modulates IBV replication. In this study, we observed down-regulation ofMSTRG.26120.58 (named lncRNA-DRNR) expression in various chicken cell lines upon IBV infection. We demonstrated that silencing lncRNA-DRNR using siRNA enhances intracellular replication of IBV. Through exploring genes encoding proteins upstream and downstream of lncRNA-DRNR within a 100 kb range, we identified chJMJD6 (chicken JMJD6) as a potential target gene negatively regulated by lncRNA-DRNR expression levels. Furthermore, chJMJD6 inhibits STAT1 methylation, thereby affecting the induction of interferon-stimulated genes (ISGs) through the activation of the IFN-β-mediated JAK-STAT signalling pathway, ultimately promoting the intracellular replication of IBV. In summary, our findings reveal the critical role played by lncRNA-DRNR during IBV infection, providing novel insights into mechanisms underlying coronavirus-induced disruption in lncRNA stability.
传染性支气管炎病毒(IBV)是传染性支气管炎(IB)的病原体,该病主要影响雏鸡,对全球家禽业构成重大挑战。了解病毒与其宿主之间的复杂相互作用对于开发创新的抗病毒策略至关重要。长链非编码 RNA(lncRNA)在调节宿主抗病毒免疫反应中起着关键作用。我们之前的研究表明,IBV 感染会破坏宿主细胞中 lncRNA 的稳定性,表明 lncRNA 在 IBV 发病机制中可能具有调节作用。lncRNA 如何精确调节 IBV 复制仍不清楚。在这项研究中,我们观察到在各种鸡细胞系中,IBV 感染后MSTRG.26120.58(命名为 lncRNA-DRNR)的表达下调。我们证明,使用 siRNA 沉默 lncRNA-DRNR 会增强 IBV 的细胞内复制。通过在 100kb 范围内探索 lncRNA-DRNR 上下游编码蛋白的基因,我们鉴定出 chJMJD6(鸡 JMJD6)是受 lncRNA-DRNR 表达水平负调控的潜在靶基因。此外,chJMJD6 抑制 STAT1 甲基化,从而通过激活 IFN-β 介导的 JAK-STAT 信号通路影响干扰素刺激基因(ISGs)的诱导,最终促进 IBV 的细胞内复制。总之,我们的研究结果揭示了 lncRNA-DRNR 在 IBV 感染过程中的关键作用,为冠状病毒诱导的 lncRNA 稳定性破坏的机制提供了新的见解。