The impact of 12C6 heavy ion irradiation-induced cellular mutations on the replication of the foot-and-mouth disease virus and the role of Cbr3

Abstract 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 12C6 heavy ion irradiation technology to process BHK-21 cells and systematic...

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Main Authors: Xiangdong Song, Shiyu Tao, Fanglan An, Xiaoming Li, Yanyan Chang, Xuerong Liu, Yan Cui
Format: Article
Language:English
Published: Springer 2025-06-01
Series:Cellular and Molecular Life Sciences
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Online Access:https://doi.org/10.1007/s00018-025-05628-6
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author Xiangdong Song
Shiyu Tao
Fanglan An
Xiaoming Li
Yanyan Chang
Xuerong Liu
Yan Cui
author_facet Xiangdong Song
Shiyu Tao
Fanglan An
Xiaoming Li
Yanyan Chang
Xuerong Liu
Yan Cui
author_sort Xiangdong Song
collection DOAJ
description Abstract 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 12C6 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 12C6 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 12C6 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.
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spelling doaj-art-e78b3cf03e1c43f2b0f908f213c5bb8a2025-08-20T02:38:14ZengSpringerCellular and Molecular Life Sciences1420-90712025-06-0182111610.1007/s00018-025-05628-6The impact of 12C6 heavy ion irradiation-induced cellular mutations on the replication of the foot-and-mouth disease virus and the role of Cbr3Xiangdong Song0Shiyu Tao1Fanglan An2Xiaoming Li3Yanyan Chang4Xuerong Liu5Yan Cui6College of Veterinary Medicine, Gansu Agricultural UniversityVaccine Process Research Laboratory, China Agricultural Vet Biology and Technology Co., LtdVaccine Process Research Laboratory, China Agricultural Vet Biology and Technology Co., LtdVaccine Process Research Laboratory, China Agricultural Vet Biology and Technology Co., LtdVaccine Process Research Laboratory, China Agricultural Vet Biology and Technology Co., LtdVaccine Process Research Laboratory, China Agricultural Vet Biology and Technology Co., LtdCollege of Veterinary Medicine, Gansu Agricultural UniversityAbstract 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 12C6 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 12C6 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 12C6 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.https://doi.org/10.1007/s00018-025-05628-612C6 heavy ionFMDVCbr3PGE2BHK-21
spellingShingle Xiangdong Song
Shiyu Tao
Fanglan An
Xiaoming Li
Yanyan Chang
Xuerong Liu
Yan Cui
The impact of 12C6 heavy ion irradiation-induced cellular mutations on the replication of the foot-and-mouth disease virus and the role of Cbr3
Cellular and Molecular Life Sciences
12C6 heavy ion
FMDV
Cbr3
PGE2
BHK-21
title The impact of 12C6 heavy ion irradiation-induced cellular mutations on the replication of the foot-and-mouth disease virus and the role of Cbr3
title_full The impact of 12C6 heavy ion irradiation-induced cellular mutations on the replication of the foot-and-mouth disease virus and the role of Cbr3
title_fullStr The impact of 12C6 heavy ion irradiation-induced cellular mutations on the replication of the foot-and-mouth disease virus and the role of Cbr3
title_full_unstemmed The impact of 12C6 heavy ion irradiation-induced cellular mutations on the replication of the foot-and-mouth disease virus and the role of Cbr3
title_short The impact of 12C6 heavy ion irradiation-induced cellular mutations on the replication of the foot-and-mouth disease virus and the role of Cbr3
title_sort impact of 12c6 heavy ion irradiation induced cellular mutations on the replication of the foot and mouth disease virus and the role of cbr3
topic 12C6 heavy ion
FMDV
Cbr3
PGE2
BHK-21
url https://doi.org/10.1007/s00018-025-05628-6
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