Liu Jinlu, Luo Shuwen, Wang Guoyao, Hu Xuming, Chen Guohong, Xu Qi
College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu Province 225009, PR China; Key Laboratory for Evaluation and Utilization of Livestock and Poultry Resources (Poultry), Ministry of Agriculture and Rural Affairs, PR China.
College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu Province 225009, PR China; Key Laboratory for Evaluation and Utilization of Livestock and Poultry Resources (Poultry), Ministry of Agriculture and Rural Affairs, PR China.
Poult Sci. 2025 Jun 12;104(9):105434. doi: 10.1016/j.psj.2025.105434.
PHB1 and PHB2, two subunits of the mitochondrial prohibitin complex, are critical regulators of antiviral innate immunity. Ducks, as natural reservoirs for RNA viruses, exhibit unique antiviral mechanisms. RIG-I is a key receptor for recognizing RNA viruses in ducks. However, the roles of PHB1 and PHB2 in the RIG-I-MAVS-IFN-β signaling pathway remain unclear. Here, we characterized the duPHB1 and PHB2 structure and functional domains, which contains similar N-terminal transmembrane domain, PHB domain and coil-coiled C-terminal domain, revealing high conservation with avian and mammalian orthologs. Both genes were ubiquitously expressed in duck tissues, with elevated levels in immune-related organs (e.g., pancreas, thymus) and tissues with high metabolic activity and tissue regeneration ability (e.g., heart, liver and muscle) post-NDV infection. We next sought to investigate the functional roles by which duPHB1 and duPHB2 triggered antiviral innate immune response. Overexpression of duPHB1/2 in DEFs enhanced MAVS activation and IFN-β production upon 5'ppp dsRNA stimulation, while siRNA-mediated knockdown suppressed these effects. Co-transfection of duPHB1 and duPHB2 synergistically amplified MAVS-dependent IFN-β induction. Crucially, MAVS depletion abolished PHB1/2-mediated IFN-β upregulation, demonstrating their dependence on MAVS signaling. Our findings establish duPHB1/2 as key regulators of mitochondrial-mediated antiviral responses in ducks, providing insights into avian innate immunity.
线粒体抑制素复合体的两个亚基PHB1和PHB2是抗病毒天然免疫的关键调节因子。鸭作为RNA病毒的天然宿主，具有独特的抗病毒机制。RIG-I是鸭体内识别RNA病毒的关键受体。然而，PHB1和PHB2在RIG-I-MAVS-IFN-β信号通路中的作用仍不清楚。在此，我们对鸭源PHB1和PHB2的结构和功能域进行了表征，其包含相似的N端跨膜结构域、PHB结构域和卷曲螺旋C端结构域，显示出与鸟类和哺乳动物直系同源物的高度保守性。这两个基因在鸭组织中普遍表达，在新城疫病毒感染后，免疫相关器官（如胰腺、胸腺）以及具有高代谢活性和组织再生能力的组织（如心脏、肝脏和肌肉）中表达水平升高。接下来，我们试图研究鸭源PHB1和鸭源PHB2触发抗病毒天然免疫反应的功能作用。在鸭胚成纤维细胞中过表达鸭源PHB1/2可增强5'ppp双链RNA刺激后MAVS的激活和IFN-β的产生，而siRNA介导的敲低则抑制了这些效应。共转染鸭源PHB1和鸭源PHB2可协同增强MAVS依赖的IFN-β诱导。至关重要的是，MAVS的缺失消除了PHB1/2介导的IFN-β上调，表明它们依赖于MAVS信号传导。我们的研究结果确定鸭源PHB1/2是鸭线粒体介导的抗病毒反应的关键调节因子，为鸟类天然免疫提供了见解。
