Disruption of Anthrax Toxin Receptor 1 in Pigs Leads to a Rare Disease Phenotype and Protection from Senecavirus A Infection

The study investigated the role of anthrax toxin receptor 1 (ANTXR1) in Senecavirus A (SVA) infection in pigs by using CRISPR/Cas9 to create ANTXR1 knockout (KO) pigs. These KO pigs displayed characteristics of GAPO syndrome, a rare human disease, and were resistant to SVA infection, showing no clinical symptoms or circulating viremia during an SVA challenge. In contrast, wild type (WT) pigs supported SVA replication and exhibited symptoms. Additionally, pigs with an in-frame (IF) mutation in ANTXR1 showed a GAPO phenotype and reduced SVA infection compared to WT pigs. The study concludes that ANTXR1 is a receptor for SVA in pigs and that its disruption can prevent SVA infection and associated clinical symptoms, offering a model for studying GAPO syndrome and SVA resistance.