Genomic regions associated with pseudorabies virus infection status in naturally infected feral swine (Sus scrofa)

Authors: BOWDEN, COURTNEY - Animal And Plant Health Inspection Service (APHIS); KISER, JENNIFER - Washington State University; MILLER, RYAN - Animal And Plant Health Inspection Service (APHIS); Buckley, Alexandra; Boggiatto, Paola; GIGLIO, RACHAEL - Animal And Plant Health Inspection Service (APHIS); BROWN, VIENNA - Animal And Plant Health Inspection Service (APHIS); GARRICK, DORIAN - Massey University; NEIBERGS, HOLLY - Washington State University; PIAGGIO, ANTIONETTE - Animal And Plant Health Inspection Service (APHIS); SPEIDEL, SCOTT - Colorado State University; SMYSER, TIMOTHY - Animal And Plant Health Inspection Service (APHIS)

Submitted to: Frontiers in Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/2/2023
Publication Date: 11/22/2023
Citation: Bowden, C.F., Kiser, J.N., Miller, R.S., Buckley, A.C., Boggiatto, P.M., Giglio, R.M., Brown, V.R., Garrick, D., Neibergs, H.L., Piaggio, A.J., Speidel, S.E., Smyser, T.J. 2023. Genomic regions associated with pseudorabies virus infection status in naturally infected feral swine (Sus scrofa). Frontiers in Genetics. https://doi.org/10.3389/fgene.2023.1292671.
DOI: https://doi.org/10.3389/fgene.2023.1292671

Interpretive Summary: Pseudorabies virus (PRV) is a herpesvirus and infection in swine can result in central nervous system, respiratory, and reproductive clinical signs, which vary in severity with age at infection. PRV has been eradicated from the United States (US) domestic swine herd, but the virus continues to circulate in feral swine populations. Feral swine populations and their distribution have expanded dramatically in recent years and are known reservoirs for PRV; thus, posing a sustained risk of disease spillover for domestic herds. Understanding the role of host genetics in infection status may offer new insights into the epidemiology and disease dynamics of PRV that can be readily applied to management strategies. Genetic mechanisms underlying host susceptibility to PRV are relatively unknown; therefore, the goal of this research was to identify loci and gene sets associated with PRV infection status among naturally infected feral swine using case/control genome-wide association studies (GWAS) and gene set enrichment analysis of single nucleotide polymorphism data (GSEA-SNP). Targeted, risk-based surveillance has been successfully implemented for pseudorabies across feral swine populations throughout the US as a part of the National Feral Swine Damage Management Program. Paired serological and genotypic data were collected from 6,081 feral swine distributed across the invaded range within the contiguous US from May 2012 to September 2020. Serum samples were tested for pseudorabies antibodies (PRV-gB ELISA) and classified as positive or negative. One intronic SNP within AKAP6 on autosome 7 was moderately associated with PRV infection status in the GWAS and various gene sets linked to metabolic pathways were enriched in the GSEA. Given the pressures and stressors that affect overall host fitness, it is not surprising that metabolic activity could be associated with PRV infection. Nevertheless, given the complexity of metabolic pathways, it is difficult to determine at this time which specific component may be involved in resistance/susceptibility to PRV infection. Ultimately, continuing to improve disease surveillance efforts in feral swine will be critical to further our understanding of the role host genetics play in PRV infection status and if PRV can be reduced in the feral swine population, the risk of spillover into commercial swine herds is lowered thus helping to secure the health of commercial pork production.

Technical Abstract: Pseudorabies virus (PRV)–the causative agent of Aujeszky’s disease–was eliminated from pig production herds in the United States (US) in 2004; however, PRV remains endemic among invasive feral swine (Sus scrofa) populations. The circulation of PRV among abundant, widespread feral swine populations poses a sustained risk for disease spillover to production herds. Pseudorabies virus has a clinical presentation associated with central nervous system disorders, respiratory illness, and reproductive losses and the reemergence of this pathogen among domestic herds would result in production costs and trade restrictions. Risk-based surveillance has been successfully implemented for PRV in feral swine populations in the US; however, understanding the role of host genetics in infection status may offer new insights into the epidemiology and disease dynamics of PRV that can be readily applied to management strategies. Genetic mechanisms underlying host susceptibility to PRV are relatively unknown; therefore, we sought to identify loci and gene sets associated with PRV infection status among naturally infected feral swine using case/control genome-wide association studies (GWAS) and gene set enrichment analysis of single nucleotide polymorphism data (GSEA-SNP). Paired serological and genotypic data were collected from 6,081 feral swine distributed across the invaded range within the contiguous US. GWAS were performed for three complementary study populations: a comprehensive population composed of feral swine throughout the invaded range within the contiguous US, populations of feral swine under high PRV infection pressure with high temporal variability, and populations of feral swine experiencing temporally stable high PRV infection pressure. We identified one intronic SNP within candidate gene AKAP6 on autosome 7. Various gene sets linked to metabolic pathways were enriched in the GSEA. Future studies would benefit from the addition of antigen detection as this information could provide a better understanding of the timing of exposure and infection status. Ultimately, continuing to improve disease surveillance efforts in feral swine will be critical to further our understanding of the role host genetics play in PRV infection status and secure the health of commercial pork production.