Foot-and-mouth disease virus activates glycolysis and hijacks HK2 to inhibit innate immunity and promote viral replication

Abstract Foot-and-mouth disease (FMD) severely restricts the healthy development of global animal husbandry, and the unclear pathogenic mechanism of FMD virus (FMDV) leads to difficulty in preventing and purifying FMD. Glycolytic remodelling is considered one of the hallmarks of viral infection, pro...

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Main Authors: Wenxian Chen, Xinyan Wang, Xiaowen Li, Weijun Wang, Yaoyao Huang, Yuwei Qin, Pengfei Liu, Keke Wu, Bingke Li, Yintao He, Sen Zeng, Lin Yi, Lianxiang Wang, Mingqiu Zhao, Hongxing Ding, Shuangqi Fan, Zhaoyao Li, Jinding Chen
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Veterinary Research
Subjects:
Online Access:https://doi.org/10.1186/s13567-025-01497-w
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author Wenxian Chen
Xinyan Wang
Xiaowen Li
Weijun Wang
Yaoyao Huang
Yuwei Qin
Pengfei Liu
Keke Wu
Bingke Li
Yintao He
Sen Zeng
Lin Yi
Lianxiang Wang
Mingqiu Zhao
Hongxing Ding
Shuangqi Fan
Zhaoyao Li
Jinding Chen
author_facet Wenxian Chen
Xinyan Wang
Xiaowen Li
Weijun Wang
Yaoyao Huang
Yuwei Qin
Pengfei Liu
Keke Wu
Bingke Li
Yintao He
Sen Zeng
Lin Yi
Lianxiang Wang
Mingqiu Zhao
Hongxing Ding
Shuangqi Fan
Zhaoyao Li
Jinding Chen
author_sort Wenxian Chen
collection DOAJ
description Abstract Foot-and-mouth disease (FMD) severely restricts the healthy development of global animal husbandry, and the unclear pathogenic mechanism of FMD virus (FMDV) leads to difficulty in preventing and purifying FMD. Glycolytic remodelling is considered one of the hallmarks of viral infection, providing energy and precursors for viral assembly and replication. In this work, the interaction and mechanism between FMDV and glycolysis were explored from the perspective of immune metabolism. We found that FMDV infection increased the extracellular acidification rate, lactic acid accumulation, and HK2 level. In addition, during FMDV infection, HK2 enhances glycolytic activity and mediates autophagic degradation of IRF3/7 to antagonize the innate immune response, thereby promoting viral replication. Our findings provide evidence that FMDV is closely correlated with host metabolism, increasing the understanding that glycolysis and HK2 facilitate virus infection, and provide new ideas for further elucidating the pathogenic mechanism of FMDV.
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institution DOAJ
issn 1297-9716
language English
publishDate 2025-04-01
publisher BMC
record_format Article
series Veterinary Research
spelling doaj-art-db4ecc17b7ed4524a4138d2ff4687dd42025-08-20T03:04:51ZengBMCVeterinary Research1297-97162025-04-0156111310.1186/s13567-025-01497-wFoot-and-mouth disease virus activates glycolysis and hijacks HK2 to inhibit innate immunity and promote viral replicationWenxian Chen0Xinyan Wang1Xiaowen Li2Weijun Wang3Yaoyao Huang4Yuwei Qin5Pengfei Liu6Keke Wu7Bingke Li8Yintao He9Sen Zeng10Lin Yi11Lianxiang Wang12Mingqiu Zhao13Hongxing Ding14Shuangqi Fan15Zhaoyao Li16Jinding Chen17College of Veterinary Medicine, South China Agricultural UniversityCollege of Veterinary Medicine, South China Agricultural UniversityCollege of Veterinary Medicine, South China Agricultural UniversityCollege of Veterinary Medicine, South China Agricultural UniversityCollege of Veterinary Medicine, South China Agricultural UniversityCollege of Veterinary Medicine, South China Agricultural UniversityState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou UniversityCollege of Veterinary Medicine, South China Agricultural UniversityCollege of Veterinary Medicine, South China Agricultural UniversityCollege of Veterinary Medicine, South China Agricultural UniversityCollege of Veterinary Medicine, South China Agricultural UniversityCollege of Veterinary Medicine, South China Agricultural UniversityWen’s Foodstuffs Group Co., Ltd.College of Veterinary Medicine, South China Agricultural UniversityCollege of Veterinary Medicine, South China Agricultural UniversityCollege of Veterinary Medicine, South China Agricultural UniversityCollege of Veterinary Medicine, South China Agricultural UniversityCollege of Veterinary Medicine, South China Agricultural UniversityAbstract Foot-and-mouth disease (FMD) severely restricts the healthy development of global animal husbandry, and the unclear pathogenic mechanism of FMD virus (FMDV) leads to difficulty in preventing and purifying FMD. Glycolytic remodelling is considered one of the hallmarks of viral infection, providing energy and precursors for viral assembly and replication. In this work, the interaction and mechanism between FMDV and glycolysis were explored from the perspective of immune metabolism. We found that FMDV infection increased the extracellular acidification rate, lactic acid accumulation, and HK2 level. In addition, during FMDV infection, HK2 enhances glycolytic activity and mediates autophagic degradation of IRF3/7 to antagonize the innate immune response, thereby promoting viral replication. Our findings provide evidence that FMDV is closely correlated with host metabolism, increasing the understanding that glycolysis and HK2 facilitate virus infection, and provide new ideas for further elucidating the pathogenic mechanism of FMDV.https://doi.org/10.1186/s13567-025-01497-wFoot-and-mouth disease virusglycolysishexokinase 2replicationinterferon regulatory factor
spellingShingle Wenxian Chen
Xinyan Wang
Xiaowen Li
Weijun Wang
Yaoyao Huang
Yuwei Qin
Pengfei Liu
Keke Wu
Bingke Li
Yintao He
Sen Zeng
Lin Yi
Lianxiang Wang
Mingqiu Zhao
Hongxing Ding
Shuangqi Fan
Zhaoyao Li
Jinding Chen
Foot-and-mouth disease virus activates glycolysis and hijacks HK2 to inhibit innate immunity and promote viral replication
Veterinary Research
Foot-and-mouth disease virus
glycolysis
hexokinase 2
replication
interferon regulatory factor
title Foot-and-mouth disease virus activates glycolysis and hijacks HK2 to inhibit innate immunity and promote viral replication
title_full Foot-and-mouth disease virus activates glycolysis and hijacks HK2 to inhibit innate immunity and promote viral replication
title_fullStr Foot-and-mouth disease virus activates glycolysis and hijacks HK2 to inhibit innate immunity and promote viral replication
title_full_unstemmed Foot-and-mouth disease virus activates glycolysis and hijacks HK2 to inhibit innate immunity and promote viral replication
title_short Foot-and-mouth disease virus activates glycolysis and hijacks HK2 to inhibit innate immunity and promote viral replication
title_sort foot and mouth disease virus activates glycolysis and hijacks hk2 to inhibit innate immunity and promote viral replication
topic Foot-and-mouth disease virus
glycolysis
hexokinase 2
replication
interferon regulatory factor
url https://doi.org/10.1186/s13567-025-01497-w
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