Zhai Xinyu, Zhang Tingting, Zhang Lan, Wang Xiuyuan, Liu Nan, Jiang Wansi, Fan Xiaole, Lu Xiaoyu, Tian Mingzhuo, Wei Liangmeng, Jiang Shijin
Sino-German Cooperative Research Centre for Zoonosis of Animal Origin of Shandong Province, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, 61 Daizong Road, Tai'an City 271018, Shandong Province, China.
Sino-German Cooperative Research Centre for Zoonosis of Animal Origin of Shandong Province, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, 61 Daizong Road, Tai'an City 271018, Shandong Province, China; College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, Guangdong Province, China; School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji'nan 250024, China.
Vet Microbiol. 2023 Dec;287:109907. doi: 10.1016/j.vetmic.2023.109907. Epub 2023 Oct 31.
Laboratory of Genetics and Physiology 2 (LGP2), along with Retinoic Acid Induced Gene-I (RIG-I) and Melanoma Differentiation Associated Gene 5, are members of the retinoic acid-inducible gene-I-like receptors (RLRs) in pattern recognition receptors, playing an important role in the host's innate immunity. Due to lacking a caspase activation and recruitment domain, LGP2 is controversially regarded as a positive or negative regulator in the antiviral response. This study aimed to explore how duck LGP2 (duLGP2) participates in duck innate immunity and its role in countering the duck Tembusu virus (DTMUV). In duck embryo fibroblast cells, the overexpression of duLGP2 significantly reduced the cell's antiviral capacity by inhibiting type I interferon (IFN) production and the expression of downstream IFN-stimulated genes. Conversely, duLGP2 knockdown had the opposite effect. For the first time, we introduced the LGP2 gene fragment into duck embryos using a lentiviral vector to ensure persistent expression and generated gene-edited ducks with LGP2 overexpression. We demonstrated that duLGP2 facilitates DTMUV replication in both in vitro and in vivo experiments, leading to robust inflammatory and antiviral responses. Interestingly, the repressive effects of duLGP2 on type I IFN production were only observed in the early stage of DTMUV infection, with type I IFN responses becoming enhanced as the viral load increased. These results indicate that duLGP2 acts as a negative regulator during the resting state and early stages of DTMUV infection. This study provides a theoretical basis for further research on duck RLRs and developing new anti-DTMUV drugs or vaccine adjuvants.
遗传学与生理学实验室2（LGP2）与视黄酸诱导基因I（RIG-I）和黑色素瘤分化相关基因5一样，是模式识别受体中视黄酸诱导基因I样受体（RLRs）的成员，在宿主先天免疫中发挥重要作用。由于缺乏半胱天冬酶激活和募集结构域，LGP2在抗病毒反应中被争议性地视为正调节因子或负调节因子。本研究旨在探讨鸭LGP2（duLGP2）如何参与鸭先天免疫及其在对抗鸭坦布苏病毒（DTMUV）中的作用。在鸭胚成纤维细胞中，duLGP2的过表达通过抑制I型干扰素（IFN）的产生和下游IFN刺激基因的表达，显著降低了细胞的抗病毒能力。相反，duLGP2的敲低则产生相反的效果。我们首次使用慢病毒载体将LGP2基因片段导入鸭胚以确保持续表达，并产生了LGP2过表达的基因编辑鸭。我们证明，duLGP2在体外和体内实验中均促进DTMUV复制，导致强烈的炎症和抗病毒反应。有趣的是，duLGP2对I型IFN产生的抑制作用仅在DTMUV感染的早期观察到，随着病毒载量的增加，I型IFN反应增强。这些结果表明，duLGP2在DTMUV感染的静止状态和早期阶段作为负调节因子发挥作用。本研究为进一步研究鸭RLRs以及开发新的抗DTMUV药物或疫苗佐剂提供了理论依据。
