Department of Animal Science, Iowa State University, Ames, IA 50011, USA.
Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
J Anim Sci. 2021 Oct 1;99(10). doi: 10.1093/jas/skab274.
Pigs with complete resistance to porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) have been produced by genetically knocking out the CD163 gene that encodes a receptor of the PRRSV for entry into macrophages. The objectives of this study were to evaluate associations of naturally occurring single nucleotide polymorphisms (SNPs) in the CD163 gene and in three other candidate genes (CD169, RGS16, and TRAF1) with host response to PRRSV-only infection and to PRRS vaccination and PRRSV/porcine circovirus 2b (PCV2b) coinfection. SNPs in the CD163 gene were not included on SNP genotyping panels that were used for previous genome-wide association analyses of these data. An additional objective was to identify the potential genetic interaction of variants at these four candidate genes with a mutation in the GBP5 gene that was previously identified to be associated with host response to PRRSV infection. Finally, the association of SNPs with expression level of the nearby gene was tested. Several SNPs in the CD163, CD169, and RGS16 genes were significantly associated with host response under PRRSV-only and/or PRRSV/PCV2b coinfection. The effects of all SNPs that were significant in the PRRSV-only infection trials depend on genetic background. The effects of some SNPs in the CD163, CD169, and RGS16 genes depend on genotype at the putative causative mutation in the GBP5 gene, which indicates a potential biological interaction of these genes with GBP5. In addition, genome-wide association results for the PRRSV-only infection trials revealed that SNPs located in the CDK5RAP2 or MEGF9 genes, near the TRAF1 gene, had suggestive effects on PRRS viral load, which indicates that these SNPs might contribute to PRRSV neuropathogenesis. In conclusion, natural genetic variants in the CD163, CD169, and RGS16 genes are associated with resistance to PRRSV and/or PCV2b infection and appear to interact with the resistance quantitative trait locus in the GBP5 gene. The identified SNPs can be used to select for increased natural resistance to PRRSV and/or PRRSV-PCV2b coinfection.
已通过基因敲除编码 PRRSV 进入巨噬细胞受体的 CD163 基因，培育出对猪繁殖与呼吸综合征（PRRS）病毒具有完全抗性的猪。本研究的目的是评估 CD163 基因和其他三个候选基因（CD169、RGS16 和 TRAF1）中的自然发生的单核苷酸多态性（SNP）与宿主对 PRRSV 单一感染以及 PRRS 疫苗接种和 PRRSV/猪圆环病毒 2b（PCV2b）共感染的反应之间的关联。在用于先前对这些数据进行全基因组关联分析的 SNP 基因分型面板中，未包括 CD163 基因中的 SNP。另一个目的是确定这些四个候选基因中的变体与先前鉴定为与 PRRSV 感染宿主反应相关的 GBP5 基因突变的潜在遗传相互作用。最后，还测试了 SNP 与附近基因表达水平的关联。在 PRRSV 单一感染和/或 PRRSV/PCV2b 共感染下，CD163、CD169 和 RGS16 基因中的几个 SNP 与宿主反应显著相关。在 PRRSV 单一感染试验中具有统计学意义的所有 SNP 的影响都取决于遗传背景。CD163、CD169 和 RGS16 基因中的一些 SNP 的影响取决于 GBP5 基因中假定致病突变的基因型，这表明这些基因与 GBP5 之间存在潜在的生物学相互作用。此外，PRRSV 单一感染试验的全基因组关联结果表明，位于 TRAF1 基因附近的 CDK5RAP2 或 MEGF9 基因中的 SNP 对 PRRS 病毒载量有提示作用，这表明这些 SNP 可能有助于 PRRSV 的神经发病机制。总之，CD163、CD169 和 RGS16 基因中的天然遗传变异与 PRRSV 和/或 PCV2b 感染的抗性有关，并且似乎与 GBP5 基因中的抗性数量性状位点相互作用。鉴定出的 SNP 可用于选择对 PRRSV 和/或 PRRSV-PCV2b 共感染的天然抗性增加。
