2. Academic Validation
  3. Foot-and-mouth disease virus activates glycolysis and hijacks HK2 to inhibit innate immunity and promote viral replication

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

  • Vet Res. 2025 Apr 1;56(1):71. doi: 10.1186/s13567-025-01497-w.
Wenxian Chen # 1,  Xinyan Wang # 1,  Xiaowen Li 1,  Weijun Wang 1,  Yaoyao Huang 1,  Yuwei Qin 1,  Pengfei Liu 2,  Keke Wu 1,  Bingke Li 1,  Yintao He 1,  Sen Zeng 1,  Lin Yi 1,  Lianxiang Wang 3,  Mingqiu Zhao 1,  Hongxing Ding 1,  Shuangqi Fan 1,  Zhaoyao Li 4 5,  Jinding Chen 6
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
  • 2 State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou University, Lanzhou, 730000, China.
  • 3 Wen's Foodstuffs Group Co., Ltd., Yunfu, Xinxing, China.
  • 4 College of Veterinary Medicine, South China Agricultural University, Guangzhou, China. lizhaoyao123@wens.com.cn.
  • 5 Wen's Foodstuffs Group Co., Ltd., Yunfu, Xinxing, China. lizhaoyao123@wens.com.cn.
  • 6 College of Veterinary Medicine, South China Agricultural University, Guangzhou, China. jdchen@scau.edu.cn.
  • # Contributed equally.
PMID: 40170113 DOI: 10.1186/s13567-025-01497-w
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.

Keywords

Foot-and-mouth disease virus; glycolysis; hexokinase 2; interferon regulatory factor; replication.

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