Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Wenjiang, 611130, China.
Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, 611130, China.
Vet Res. 2022 Mar 18;53(1):22. doi: 10.1186/s13567-022-01043-y.
Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are cytosolic pattern recognition receptors that initiate innate antiviral immunity. Recent reports found that duck RLRs significantly restrict duck plague virus (DPV) infection. However, the molecular mechanism by which DPV evades immune responses is unknown. In this study, we first found that the DPV UL41 protein inhibited duck interferon-β (IFN-β) production mediated by RIG-I and melanoma differentiation-associated gene 5 (MDA5) by broadly downregulating the mRNA levels of important adaptor molecules, such as RIG-I, MDA5, mitochondrial antiviral signalling protein (MAVS), stimulator of interferon gene (STING), TANK-binding kinase 1 (TBK1), and interferon regulatory factor (IRF) 7. The conserved sites of the UL41 protein, E229, D231, and D232, were responsible for this activity. Furthermore, the DPV CHv-BAC-ΔUL41 mutant virus induced more duck IFN-β and IFN-stimulated genes (Mx, OASL) production in duck embryo fibroblasts (DEFs) than DPV CHv-BAC parent virus. Our findings provide insights into the molecular mechanism underlying DPV immune evasion.
视黄酸诱导基因 I（RIG-I）样受体（RLRs）是细胞溶质模式识别受体，可启动先天抗病毒免疫。最近的报道发现，鸭 RLRs 可显著限制鸭瘟病毒（DPV）感染。然而，DPV 逃避免疫反应的分子机制尚不清楚。在这项研究中，我们首先发现，DPV UL41 蛋白通过广泛地下调 RIG-I 和黑色素瘤分化相关基因 5（MDA5）的重要衔接分子（如 RIG-I、MDA5、线粒体抗病毒信号蛋白（MAVS）、干扰素基因刺激因子（STING）、TANK 结合激酶 1（TBK1）和干扰素调节因子（IRF）7 的 mRNA 水平，来抑制 RIG-I 和 MDA5 介导的鸭干扰素-β（IFN-β）产生。UL41 蛋白的保守位点 E229、D231 和 D232 负责此活性。此外，与 DPV CHv-BAC 亲本病毒相比，DPV CHv-BAC-ΔUL41 突变病毒在鸭胚成纤维细胞（DEFs）中诱导更多的鸭 IFN-β 和干扰素刺激基因（Mx、OASL）产生。我们的研究结果提供了对 DPV 免疫逃避的分子机制的深入了解。
