Song Xiangdong, Tao Shiyu, An Fanglan, Li Xiaoming, Chang Yanyan, Liu Xuerong, Cui Yan
College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China.
Vaccine Process Research Laboratory, China Agricultural Vet Biology and Technology Co., Ltd, Lanzhou, China.
Cell Mol Life Sci. 2025 Jun 28;82(1):261. doi: 10.1007/s00018-025-05628-6.
Foot-and-mouth disease (FMD) is an infectious disease in animals caused by the foot-and-mouth disease virus (FMDV). However, the mechanism of FMDV infection in host cells remains unclear. In this study, we utilized C heavy ion irradiation technology to process BHK-21 cells and systematically screened and evaluated cell lines with distinct virus replication characteristics. We subsequently employed proteomics to detect the differences between these cell lines and the control BHK-21 cell line following C heavy ion irradiation. Both cell lines exhibited common downregulation of cell adhesion molecules but also exhibited distinct upregulation pathways. In terms of immune and metabolic responses, BHK-5 infection triggered an immune response, including the upregulation of cytokine-cytokine receptor signaling pathways and lysosome-related pathways, while the upregulation of drug metabolism pathways enhanced the ability to metabolize exogenous substances. Conversely, BHK-7 infection tended to promote metabolic pathway changes that favor virus replication, such as the upregulation of folate biosynthesis, polysaccharide degradation, and linolenic acid metabolism pathways. Additionally, we observed significant downregulation of Cbr3 in cell lines that promoted virus replication and significant upregulation in those that inhibited virus replication. Upon validating the results in Cbr3 knockout cells, we found that knocking out Cbr3 could increase FMDV replication by increasing the cellular content of prostaglandin E2 (PGE2), suggesting a close relationship between FMDV replication and PGE2 levels. This method can increase the production efficiency of FMDV vaccines while reducing manufacturing costs. This study innovatively employed C heavy ion irradiation technology to induce cell transformation and explored its impact on FMDV, offering a new perspective for understanding virus replication mechanisms and potentially providing a target and idea for developing novel antiviral strategies.
口蹄疫（FMD）是由口蹄疫病毒（FMDV）引起的动物传染病。然而，FMDV在宿主细胞中的感染机制仍不清楚。在本研究中，我们利用碳重离子辐照技术处理BHK - 21细胞，并系统筛选和评估具有不同病毒复制特征的细胞系。随后，我们采用蛋白质组学方法检测这些细胞系与经碳重离子辐照的对照BHK - 21细胞系之间的差异。两种细胞系均表现出细胞粘附分子的共同下调，但也表现出不同的上调途径。在免疫和代谢反应方面，BHK - 5感染引发了免疫反应，包括细胞因子 - 细胞因子受体信号通路和溶酶体相关通路的上调，而药物代谢通路的上调增强了对外源物质的代谢能力。相反，BHK - 7感染倾向于促进有利于病毒复制的代谢途径变化，如叶酸生物合成、多糖降解和亚麻酸代谢途径的上调。此外，我们观察到在促进病毒复制的细胞系中Cbr3显著下调，而在抑制病毒复制的细胞系中显著上调。在Cbr3基因敲除细胞中验证结果时，我们发现敲除Cbr3可通过增加前列腺素E2（PGE2）的细胞含量来增加FMDV复制，这表明FMDV复制与PGE2水平密切相关。该方法可提高FMDV疫苗的生产效率，同时降低制造成本。本研究创新性地利用碳重离子辐照技术诱导细胞转化，并探索其对FMDV的影响，为理解病毒复制机制提供了新的视角，并可能为开发新型抗病毒策略提供靶点和思路。
