Li Xuan, Gu Wenyuan, Li Shitao, Fiorito Filomena, Ding Xiuyan, Zhu Liqian
Key Laboratory of Microbial Diversity Research and Application of Hebei Province, School of Life Sciences, Hebei University, Baoding, 071002, China.
Center for Animal Diseases Control and Prevention of Hebei Province, Shijiazhuang, 050035, China.
Vet Res. 2025 Mar 7;56(1):50. doi: 10.1186/s13567-025-01480-5.
Bovine herpesvirus 1 (BoHV-1) productive infection stimulates β-catenin-dependent transcription to facilitate virus replication. Phosphoglycerate kinase 1 (PGK1), which catalyses the initial step of ATP production during glycolysis, also has a mitochondrial form that is implicated in tissue injury across various diseases. However, the relationship between BoHV-1 replication and the PGK1 signalling pathway is not yet fully understood. In this study, we discovered that PGK1 signalling significantly influences BoHV-1 replication, with the virus infection leading to a marked increase in the accumulation of PGK1 proteins in mitochondria. Overexpression of β-catenin reduces PGK1 steady-state protein levels while overexpressing PGK1 boosts β-catenin protein expression-a phenomenon that reverses upon virus infection. Importantly, consistent with PGK1's vital role in virus replication, PGK1 stimulates β-catenin-dependent transcriptional activity, partly by promoting the nuclear accumulation of transcriptionally active β-catenin and phospho-β-catenin (S552) in virus-infected cells. In summary, our findings suggest for the first time that PGK1 signalling may be involved in BoHV-1 replication and contribute to virus pathogenicity.
牛疱疹病毒1型（BoHV-1）的增殖性感染会刺激β-连环蛋白依赖性转录，以促进病毒复制。磷酸甘油酸激酶1（PGK1）催化糖酵解过程中ATP生成的起始步骤，它也有一种线粒体形式，与多种疾病中的组织损伤有关。然而，BoHV-1复制与PGK1信号通路之间的关系尚未完全明确。在本研究中，我们发现PGK1信号通路对BoHV-1复制有显著影响，病毒感染会导致线粒体中PGK1蛋白积累显著增加。β-连环蛋白的过表达会降低PGK1的稳态蛋白水平，而PGK1的过表达则会提高β-连环蛋白的蛋白表达——这种现象在病毒感染后会逆转。重要的是，与PGK1在病毒复制中的关键作用一致，PGK1会刺激β-连环蛋白依赖性转录活性，部分是通过促进病毒感染细胞中转录活性β-连环蛋白和磷酸化β-连环蛋白（S552）的核积累来实现的。总之，我们的研究结果首次表明，PGK1信号通路可能参与BoHV-1复制并促进病毒致病性。
