Xiaomiao Hu, Ruihong Zhao, Wei Li, Xiaocheng Pan, Yin Dai, Huimin Wu, Yantao Wu, Chengcheng Zhang
Institute of Animal Husbandry and Veterinary Medicine, Anhui Academy of Agricultural Sciences/Livestock and Poultry Epidemic Diseases Research Center of Anhui Province/Anhui province Key laboratory of Livestock and Poultry Product Safety Engineering, Hefei, Anhui 230031, China.
Yangzhou Polytechnic College, Yangzhou 225009, China.
Poult Sci. 2025 Jan;104(1):104582. doi: 10.1016/j.psj.2024.104582. Epub 2024 Nov 28.
Avian reovirus (ARV) is highly prevalent in healthy poultry flocks and has been linked to viral arthritis/tendonitis, dwarf syndrome, chronic respiratory disease, and immunosuppression in avian species, resulting in significant economic losses within the poultry industry. The non-structural protein p17 encoded by ARV induces cellular autophagy and facilitates viral proliferation, playing a pivotal role in viral pathogenesis. To further elucidate the pathogenic mechanism basis of ARV p17 protein function, we employed a yeast two-hybrid system to identify Phosphoribosyl pyrophosphate synthetase 2 (PRPS2) as an interacting host protein with p17. In this study, we validated the interaction between PRPS2 and p17 using laser confocal microscopy, coimmunoprecipitation, and GST-Pulldown assays. Moreover, our findings demonstrate that the C-terminal region of PRPS2 is responsible for its binding to the p17 protein. Intriguingly, ARV infection significantly upregulated PRPS2 expression levels. Additionally, PRPS2 was shown to have a substantial impact on ARV replication; overexpression of PRPS2 increased ARV replication while knockdown of PRPS2 resulted in decreased quantities of ARV particles. Furthermore, our findings suggest that this process involves cellular apoptosis as a potential mechanism underlying these observations. Overall, this research provides valuable insights into elucidating the function of the p17 protein and sheds light on the pathogenic mechanism involving ARV-induced cellular apoptosis while offering novel perspectives for exploring therapeutic targets against ARV.
禽呼肠孤病毒（ARV）在健康家禽群体中高度流行，并与禽类的病毒性关节炎/肌腱炎、侏儒综合征、慢性呼吸道疾病和免疫抑制有关，给家禽业造成了重大经济损失。ARV编码的非结构蛋白p17诱导细胞自噬并促进病毒增殖，在病毒发病机制中起关键作用。为了进一步阐明ARV p17蛋白功能的致病机制基础，我们利用酵母双杂交系统鉴定出磷酸核糖焦磷酸合成酶2（PRPS2）是与p17相互作用的宿主蛋白。在本研究中，我们使用激光共聚焦显微镜、免疫共沉淀和GST下拉实验验证了PRPS2与p17之间的相互作用。此外，我们的研究结果表明，PRPS2的C末端区域负责其与p17蛋白的结合。有趣的是，ARV感染显著上调了PRPS2的表达水平。此外，PRPS2对ARV复制有重大影响；PRPS2的过表达增加了ARV的复制，而敲低PRPS2则导致ARV颗粒数量减少。此外，我们的研究结果表明，这一过程涉及细胞凋亡，这可能是这些观察结果的潜在机制。总体而言，本研究为阐明p17蛋白的功能提供了有价值的见解，揭示了ARV诱导细胞凋亡的致病机制，同时为探索抗ARV治疗靶点提供了新的视角。
