DNAJC14 gene-edited pigs are resistant to classical pestiviruses

Area of Science:

• Veterinary Virology
• Molecular Biology
• Livestock Genetics

Background:

• Infectious diseases significantly hinder livestock productivity and welfare.
• Classical pestiviruses, including classical swine fever virus (CSFV), cause substantial economic losses in agriculture.
• The host protein DNAJC14 is crucial for the replication of classical pestiviruses.

Purpose of the Study:

• To investigate the role of DNAJC14 in pestivirus replication.
• To develop pestivirus-resistant livestock using gene editing technology.
• To assess the efficacy of targeting DNAJC14 for disease control.

Main Methods:

• Utilized CRISPR/Cas9 gene editing to modify the DNAJC14 gene in pigs.
• Cultured primary cells from edited pigs for in vitro virus replication assays.
• Challenged gene-edited pigs with classical swine fever virus (CSFV) for in vivo efficacy assessment.

Main Results:

• Primary cells from pigs with altered DNAJC14 expression did not support CSFV or bovine viral diarrhoea virus (BVDV) replication.
• Gene-edited pigs exhibited complete resistance to in vivo CSFV challenge.
• Demonstrated the essential role of DNAJC14 in pestivirus infection.

Conclusions:

• CRISPR/Cas9-mediated gene editing of DNAJC14 confers robust resistance to classical pestiviruses in pigs.
• Targeting host-pathogen interactions via gene editing offers a promising strategy for controlling livestock viral diseases.
• This approach provides a novel tool for enhancing biosecurity in swine farming and preventing significant economic losses.