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Prolyl endopeptidase is a multifunctional host factor required for FMDV infection
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Journal Article
Prolyl endopeptidase is a multifunctional host factor required for FMDV infection
2025
Overview
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.
Publisher
Springer International Publishing,Springer Nature B.V,Springer
Subject
/ Animals
/ Biomedical and Life Sciences
/ CRISPR
/ DEAD Box Protein 58 - genetics
/ DEAD Box Protein 58 - metabolism
/ Foot-and-Mouth Disease - genetics
/ Foot-and-Mouth Disease - metabolism
/ Foot-and-Mouth Disease - virology
/ Foot-and-mouth disease virus
/ Foot-and-Mouth Disease Virus - pathogenicity
/ Foot-and-Mouth Disease Virus - physiology
/ Genes
/ Genomes
/ Humans
/ Interferon-Induced Helicase, IFIH1 - genetics
/ Interferon-Induced Helicase, IFIH1 - metabolism
/ Mice
/ mRNA
/ Original
/ Prolyl Oligopeptidases - genetics
/ Prolyl Oligopeptidases - metabolism
/ Proteins
/ RNA-Binding Proteins - genetics
/ RNA-Binding Proteins - metabolism
/ Serine Endopeptidases - genetics
/ Serine Endopeptidases - metabolism
/ Viruses
