Ji Likai, Liu Qianqian, Wang Na, Wang Yan, Sun Jianhe, Yan Yaxian
School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China; School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai, People's Republic of China.
School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai, People's Republic of China.
Vet Microbiol. 2022 Sep;272:109515. doi: 10.1016/j.vetmic.2022.109515. Epub 2022 Jul 19.
Innate immune system composed of pathogen pattern recognition receptors (PRRs) is the first barrier to recognize and defend viral invasion. Previously，the double-stranded RNA binding protein staufen1 (STAU1) was identified as an important candidate in regulating RIG-I/MDA5 signaling axis, which is the major cytosolic PRRs for initiating immune response to antagonize RNA viruses. However, the mechanism of STAU1 on RNA virus infection is still unclear. In the present study, we demonstrated that STAU1 is a highly conservative dsRNA-binding protein in human and mammals. The porcine STAU1 (pSTAU1) could bind to the PEDV original dsRNA in cytoplasm. Furthermore, pSTAU1 is a binding partner that can positively increase the combination of MDA5 and dsRNA in cells, but slightly on RIG-I-dsRNA binding. Moreover, knockdown pSTAU1 led to inhibition of poly(I:C)-stimulated, VSV and RIG-I/MDA5-induced activation of porcine INF-β promotor activation. Overexpression pSTAU1 could positively suppress the VSV proliferation in 3D4/21 cells. In sum, our data identify pSTAU1 as a key component of RIG-I/MDA5 binding viral dsRNA required for innate antiviral immunity in swine. The novel findings provide a new insight into host sensing the RNA-viruses infection.
由病原体模式识别受体（PRRs）组成的先天免疫系统是识别和抵御病毒入侵的第一道防线。此前，双链RNA结合蛋白Staufen1（STAU1）被确定为调节RIG-I/MDA5信号轴的重要候选者，RIG-I/MDA5信号轴是启动免疫反应以对抗RNA病毒的主要胞质PRRs。然而，STAU1对RNA病毒感染的机制仍不清楚。在本研究中，我们证明STAU1是人和哺乳动物中一种高度保守的双链RNA结合蛋白。猪STAU1（pSTAU1）可与细胞质中的PEDV原始双链RNA结合。此外，pSTAU1是一种结合伴侣，可正向增加细胞中MDA5与双链RNA的结合，但对RIG-I-双链RNA结合的影响较小。此外，敲低pSTAU1会导致聚肌苷酸:聚胞苷酸（poly(I:C)）刺激、水泡性口炎病毒（VSV）和RIG-I/MDA5诱导的猪干扰素-β（INF-β）启动子激活受到抑制。过表达pSTAU1可正向抑制VSV在3D4/21细胞中的增殖。总之，我们的数据确定pSTAU1是猪先天抗病毒免疫中RIG-I/MDA5结合病毒双链RNA所需的关键成分。这些新发现为宿主感知RNA病毒感染提供了新的见解。
