<p>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 <i>PREP</i> knockout (<i>PREP</i>-KO) significantly enhances host resistance to FMDV infection by upregulating the expression of <i>RIG-I</i> and <i>MDA5</i> mRNA. Specifically, <i>PREP</i>-KO destabilizes the PUM1 protein via proteasomal and apoptotic degradation pathways, thereby increasing <i>RIG-I</i> promoter activity. Additionally, <i>PREP</i>-KO inhibits the FMDV life cycle at the replication stage. <i>In vivo</i> 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.</p>

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Prolyl endopeptidase is a multifunctional host factor required for FMDV infection

  • Kun Ma,
  • Rongzeng Hao,
  • Tianran Liu,
  • Yi Ru,
  • Tao Feng,
  • Xiaolan Qi,
  • Yuzhe Wang,
  • Bingzhou Lu,
  • Sen Wu,
  • Dan Li,
  • Ran Zhang,
  • Yaofeng Zhao,
  • Haixue Zheng

摘要

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.