2. Academic Validation
  3. Prolyl endopeptidase is a multifunctional host factor required for FMDV infection

Prolyl endopeptidase is a multifunctional host factor required for FMDV infection

  • Cell Mol Life Sci. 2025 Nov 19;82(1):408. doi: 10.1007/s00018-025-05941-0.
Kun Ma # 1 2,  Rongzeng Hao # 2,  Tianran Liu 1,  Yi Ru 2,  Tao Feng 2,  Xiaolan Qi 2,  Yuzhe Wang 1,  Bingzhou Lu 2,  Sen Wu 1,  Dan Li 2,  Ran Zhang 3,  Yaofeng Zhao 4,  Haixue Zheng 5
Affiliations

Affiliations

  • 1 Frontiers Science Center for Molecular Design Breeding, State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing, 100193, China.
  • 2 State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.
  • 3 Frontiers Science Center for Molecular Design Breeding, State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing, 100193, China. [email protected].
  • 4 Frontiers Science Center for Molecular Design Breeding, State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing, 100193, China. [email protected].
  • 5 State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China. [email protected].
  • # Contributed equally.
PMID: 41258568 DOI: 10.1007/s00018-025-05941-0
Abstract

Foot-and-mouth disease virus (FMDV) poses a significant global threat to livestock production, underscoring the urgent need for a deeper understanding of virus-host interactions to develop effective prevention strategies. In this study, we identify prolyl endopeptidase (PREP) as a critical host factor in FMDV Infection. We demonstrate that PREP knockout (PREP-KO) significantly enhances host resistance to FMDV Infection by upregulating the expression of RIG-I and MDA5 mRNA. Specifically, PREP-KO destabilizes the PUM1 protein via proteasomal and apoptotic degradation pathways, thereby increasing RIG-I promoter activity. Additionally, PREP-KO inhibits the FMDV life cycle at the replication stage. In vivo experiments further reveal that PREP inhibition or knockout provides protection against FMDV Infection following a sublethal challenge in mice. Our findings identify PREP as a novel Antiviral target, providing valuable insights for development of Antiviral therapies and breeding of disease-resistant livestock.

Keywords

Foot-and-mouth disease virus; Innate immunity; Prolyl endopeptidase; Pumilio protein 1; Virus life cycle.

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