Li Shasha, Wang Linhao, Wen Yanqiao, Han Jinyuan, Hou Jixia, Hou Zhengyang, Xie Jingying, Li Huixia, Li Xiangrong, Yang Yanmei, Feng Ruofei
Engineering Research Center of Key Technology and Industrialization of Cell-based Vaccine, Ministry of Education, Biomedical Research Center, Northwest Minzu University, Lanzhou, 730030, China; Key Laboratory of Biotechnology and Bioengineering of State Ethnic Affairs Commission, Biomedical Research Center, Northwest Minzu University, Lanzhou, 730030, China; School of Life Sciences and Engineering, Northwest Minzu University, Lanzhou, 730030, China.
Key Laboratory of Biotechnology and Bioengineering of State Ethnic Affairs Commission, Biomedical Research Center, Northwest Minzu University, Lanzhou, 730030, China.
Virology. 2025 Apr;605:110451. doi: 10.1016/j.virol.2025.110451. Epub 2025 Feb 12.
Porcine epidemic diarrhea virus (PEDV) is enteropathogenic coronavirus, and mainly damages intestines, causing diarrhea, vomiting, anorexia, and depression. PEDV highly pathogenic strains spread rapidly and pose significant economic and public health concerns in our country. After virus invasion, RIG-I detects viral double-stranded RNA to activate antiviral innate immunity, inducing IFN responses. PEDV genome encodes 16 non-structure proteins (nsp1-nsp16). These nsps have been effectively involved in the interaction of PEDV and host. PEDV nsp14 is a bi-functional enzyme that is responsible for proofreading and RNA cap G-N-7 methylation during viral infection. In this study, we confirmed that PEDV nsp14 was an interferon antagonist and inhibited IFN production induced by SeV and Poly(I:C). Further, we declared that PEDV infection decreased protein level of RIG-I, and the PEDV nsp14 played a part in this inhibitory effect. PEDV nsp14 induced cell apoptosis and then degraded RIG-I through caspase 8 and caspase 9 pathway during PEDV infection. The N7 MTase domain was critical for nsp14-mediated degradation of RIG-I. Our results revealed the novel function of PEDV nsp14 in virus-host interaction and provided a potential antiviral drug target.
猪流行性腹泻病毒（PEDV）是一种肠道致病性冠状病毒，主要损害肠道，引起腹泻、呕吐、厌食和抑郁。PEDV高致病性毒株传播迅速，在我国引起了重大的经济和公共卫生问题。病毒入侵后，维甲酸诱导基因I（RIG-I）检测病毒双链RNA以激活抗病毒天然免疫，诱导干扰素反应。PEDV基因组编码16种非结构蛋白（nsp1-nsp16）。这些非结构蛋白有效地参与了PEDV与宿主的相互作用。PEDV nsp14是一种双功能酶，在病毒感染期间负责校对和RNA帽G-N-7甲基化。在本研究中，我们证实PEDV nsp14是一种干扰素拮抗剂，可抑制仙台病毒（SeV）和聚肌苷酸-聚胞苷酸（Poly(I:C)）诱导的干扰素产生。此外，我们发现PEDV感染降低了RIG-I的蛋白水平，并且PEDV nsp14在这种抑制作用中发挥了作用。在PEDV感染期间，PEDV nsp14通过半胱天冬酶8和半胱天冬酶9途径诱导细胞凋亡，进而降解RIG-I。N7甲基转移酶结构域对于nsp14介导的RIG-I降解至关重要。我们的研究结果揭示了PEDV nsp14在病毒-宿主相互作用中的新功能，并提供了一个潜在的抗病毒药物靶点。
