Wang Ke, Huang Manzi, Zeng Qinghua, Wu Huansheng
Department of Veterinary Preventive Medicine, College of Animal Science and Technology, Jiangxi Agricultural University, Zhimin Street, Qingshan Lake, Nanchang, 330045, PR China; Jiangxi Provincial Key laboratory for Animal Science and Technology, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, PR China.
Department of Veterinary Preventive Medicine, College of Animal Science and Technology, Jiangxi Agricultural University, Zhimin Street, Qingshan Lake, Nanchang, 330045, PR China; Jiangxi Provincial Key laboratory for Animal Science and Technology, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, PR China.
Poult Sci. 2025 Mar;104(3):104859. doi: 10.1016/j.psj.2025.104859. Epub 2025 Jan 28.
While the role of hnRNP proteins in modulating interferon signaling and virus replication in mammals has been extensively studied, the impact of chicken hnRNPs on innate immune response and Infectious Bursal Disease Virus (IBDV) replication remains largely unexplored. In this study, multiple chicken hnRNPs were identified to interact with genomic dsRNA. Initially, these hnRNPs were found to be exclusively localized in the nucleus before IBDV infection. However, post-infection, they translocated into the cytoplasm to co-localize with the viral dsRNA. Furthermore, the effects of various chicken hnRNPs on IFN-β activation, induced by the chicken MDA5-MAVS-TBK1 and STING-IRF7 pathway, were analyzed. Among these hnRNPs, hnRNPA3 demonstrated the most significant reduction in inhibiting IFN-β activation at the MAVS step. Additionally, overexpression of chicken hnRNPA3 was found to markedly enhance IBDV replication. Conversely, silencing chicken hnRNPA3 via siRNA significantly increased IFN-β production, thereby substantially suppressing IBDV replication. In summary, our findings reveal for the first time that multiple chicken hnRNPs interact with viral dsRNA, modulate IFN-β production, and specifically, that chicken hnRNPA3 promotes IBDV replication. These insights into the role of chicken hnRNPs in viral replication and immune response could pave the way for new therapeutic strategies against IBDV.
虽然hnRNP蛋白在调节哺乳动物干扰素信号传导和病毒复制中的作用已得到广泛研究,但鸡hnRNP对先天免疫反应和传染性法氏囊病病毒(IBDV)复制的影响在很大程度上仍未得到探索。在本研究中,鉴定出多种鸡hnRNP与基因组双链RNA相互作用。最初,这些hnRNP在IBDV感染前仅定位于细胞核。然而,感染后,它们转移到细胞质中与病毒双链RNA共定位。此外,分析了各种鸡hnRNP对由鸡MDA5-MAVS-TBK1和STING-IRF7途径诱导的IFN-β激活的影响。在这些hnRNP中,hnRNPA3在MAVS步骤抑制IFN-β激活方面表现出最显著的降低。此外,发现鸡hnRNPA3的过表达显著增强IBDV复制。相反,通过siRNA沉默鸡hnRNPA3显著增加IFN-β的产生,从而大幅抑制IBDV复制。总之,我们的研究结果首次揭示了多种鸡hnRNP与病毒双链RNA相互作用,调节IFN-β的产生,具体而言,鸡hnRNPA3促进IBDV复制。这些对鸡hnRNP在病毒复制和免疫反应中作用的见解可能为针对IBDV的新治疗策略铺平道路。