Table1_Genomic regions associated with pseudorabies virus infection status in naturally infected feral swine (Sus scrofa).docx

Pseudorabies virus (PRV)—the causative agent of Aujeszky’s disease—was eliminated from commercial pig production herds in the United States (US) in 2004; however, PRV remains endemic among invasive feral swine (Sus scrofa). The circulation of PRV among abundant, widespread feral swine populations poses a sustained risk for disease spillover to production herds. 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 applied to management strategies. Genetic mechanisms underlying host susceptibility to PRV are relatively unknown; therefore, we sought to identify genomic regions associated with PRV infection status among naturally infected feral swine using 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. Three complementary study populations were developed for GWAS: 1) comprehensive population consisting of feral swine throughout the invaded range within the contiguous US; 2) population of feral swine under high, but temporally variable PRV infection pressure; and 3) population of feral swine under temporally stable, high PRV infection pressure. We identified one intronic SNP associated with PRV infection status within candidate gene AKAP6 on autosome 7. Various gene sets linked to metabolic pathways were enriched in the GSEA–SNP. Ultimately, improving disease surveillance efforts in feral swine will be critical to further understanding of the role host genetics play in PRV infection status, helping secure the health of commercial pork production.

伪狂犬病病毒（Pseudorabies virus, PRV）是奥耶斯基病的病原体，美国已于2004年在商业猪生产群中清除该病毒；但目前入侵性野猪（Sus scrofa）种群中仍存在PRV的地方性流行。当前野猪种群数量庞大且分布广泛，其中PRV的持续循环对商业猪群构成持续的疾病溢出风险。美国已针对野猪种群中的PRV成功实施基于风险的监测方案。然而，阐明宿主遗传学在感染状态中的作用，可为PRV的流行病学与疾病动态研究提供新视角，进而为管理策略制定提供依据。宿主对PRV的易感性遗传机制目前尚不明晰。为此，本研究借助全基因组关联分析（genome–wide association studies, GWAS）与单核苷酸多态性数据基因集富集分析（gene set enrichment analysis of single nucleotide polymorphism data, GSEA–SNP），旨在自然感染的野猪种群中筛选与PRV感染状态相关的基因组区域。研究采集了美国本土入侵范围内6081头野猪的配对血清学与基因型数据。基于此构建了3个互补的研究种群用于GWAS分析：1）覆盖美国本土入侵全境的野猪综合种群；2）暴露于高强度但时间动态变化的PRV感染压力的野猪种群；3）暴露于时间稳定且高强度PRV感染压力的野猪种群。本研究在7号常染色体上的候选基因AKAP6内，发现了一个与PRV感染状态显著相关的内含子单核苷酸多态性（SNP）。GSEA–SNP分析显示，多条与代谢通路相关的基因集存在富集现象。综上，优化野猪的疾病监测工作，对于进一步阐明宿主遗传学在PRV感染中的作用至关重要，将有助于保障商业猪肉产业的健康发展。