Prolyl endopeptidase is a multifunctional host factor required for FMDV infection

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Foot-and-mouth disease virus (FMDV) causes significant global livestock losses.
• Understanding virus-host interactions is crucial for developing FMDV prevention strategies.

Purpose of the Study:

• To identify host factors involved in FMDV infection.
• To investigate the role of prolyl endopeptidase (PREP) in FMDV pathogenesis.

Main Methods:

• Utilized PREP knockout (PREP-KO) cell and mouse models.
• Assessed changes in RIG-I and MDA5 mRNA expression.
• Investigated PUM1 protein stability and RIG-I promoter activity.
• Evaluated FMDV replication and in vivo protection.

Main Results:

• PREP-KO significantly enhanced host resistance to FMDV.
• PREP-KO upregulated RIG-I and MDA5 mRNA expression.
• PREP-KO led to PUM1 protein degradation, increasing RIG-I promoter activity.
• PREP inhibition or knockout protected mice against FMDV infection.

Conclusions:

• PREP is a critical host factor that supports FMDV replication.
• PREP is a novel antiviral target for FMDV.
• Findings support the development of antiviral therapies and disease-resistant livestock breeds.