Zhu Huixin, Lou Jinxiu, Yang Zhen, Bai Juan, Jiang Ping, Wang Xianwei, Liu Xing
Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
J Virol. 2025 Mar 18;99(3):e0001825. doi: 10.1128/jvi.00018-25. Epub 2025 Feb 13.
Porcine epidemic diarrhea virus (PEDV), a highly pathogenic enteric coronavirus, has caused significant economic losses worldwide in recent years. The PEDV spike (S) protein has been reported to undergo extensive N-glycosylation, suggesting that glycosylation plays a crucial role in PEDV replication. In this study, we demonstrated that the N-glycosylation pathway promotes PEDV replication by facilitating the glycosylation of the S protein. First, we observed that pharmacological inhibition of host N-glycosylation using specific inhibitors significantly reduces viral replication. Furthermore, genetic ablation of STT3A or STT3B, the catalytically active subunits of the oligosaccharyltransferase (OST) complex, revealed that the STT3B-OST complex, but not STT3A, is preferentially required for PEDV replication. Notably, we showed that the N-glycosylation of the PEDV S protein depends on the oligosaccharyltransferase activity of STT3B. Together, the study demonstrated the critical role of the N-glycosylation pathway in PEDV replication by elucidating the relationship between the N-glycosylation of the PEDV S protein and STT3B, thereby presenting a potential new target for the prevention and control of PEDV.IMPORTANCEThe highly N-glycosylated spike protein of porcine epidemic diarrhea virus (PEDV) is a multifunctional protein that plays a crucial role in the viral replication cycle. In this study, using pharmacological inhibitors, we demonstrated the importance of the N-glycosylation pathway in PEDV replication. Genetic analysis revealed that STT3B, one of the catalytically active subunits of the oligosaccharyltransferase complex, promotes viral proliferation by regulating the N-glycosylation of the PEDV spike protein. Our findings enhance the understanding of the role of the N-glycosylation pathway in viral infection and identify STT3B as a potential therapeutic target for controlling PEDV infection.
猪流行性腹泻病毒（PEDV）是一种高致病性肠道冠状病毒，近年来在全球范围内造成了重大经济损失。据报道，PEDV刺突（S）蛋白经历广泛的N-糖基化，这表明糖基化在PEDV复制中起关键作用。在本研究中，我们证明N-糖基化途径通过促进S蛋白的糖基化来促进PEDV复制。首先，我们观察到使用特异性抑制剂对宿主N-糖基化进行药理学抑制可显著降低病毒复制。此外，对寡糖基转移酶（OST）复合物的催化活性亚基STT3A或STT3B进行基因敲除，结果表明，PEDV复制优先需要STT3B-OST复合物，而不是STT3A。值得注意的是，我们发现PEDV S蛋白的N-糖基化取决于STT3B的寡糖基转移酶活性。总之，该研究通过阐明PEDV S蛋白的N-糖基化与STT3B之间的关系，证明了N-糖基化途径在PEDV复制中的关键作用，从而为PEDV的预防和控制提供了一个潜在的新靶点。
重要性
猪流行性腹泻病毒（PEDV）高度N-糖基化的刺突蛋白是一种多功能蛋白，在病毒复制周期中起关键作用。在本研究中，我们使用药理学抑制剂证明了N-糖基化途径在PEDV复制中的重要性。遗传分析表明，寡糖基转移酶复合物的催化活性亚基之一STT3B通过调节PEDV刺突蛋白的N-糖基化来促进病毒增殖。我们的研究结果加深了对N-糖基化途径在病毒感染中作用的理解，并确定STT3B为控制PEDV感染的潜在治疗靶点。
