Biological Evidence for Genomic Regions Associated with Host Response to Co-Infection with PRRS Virus and PCV2b in Commercial Nursery Pigs

Previously, a major quantitative trait locus (QTL) for host response to porcine reproductive and respiratory syndrome (PRRS) was identified on chromosome (SSC) 4. The WUR10000125 (WUR) single nucleotide polymorphism (SNP) is used as a tag SNP for this QTL. The objectives of this study were to identify genomic regions (other than WUR) associated with average daily gain (ADG) and viral load (VL) following co-infection with PRRS virus (PRRSV) and porcine circovirus type 2b (PCV2b) and to assess the biological relevance of these regions.

Data originated from two trials of 200 pigs each. Pigs from the same genetic source were pre-selected (half AA/half AB) for WUR SNP genotype since the “B” allele is completely dominant. At weaning, pigs were sorted into one of two rooms and pigs in one room received a modified live PRRSV vaccine 28 days prior (Pre Co-X) to co-infecting all pigs with PRRSV and PCV2b (Post Co-X). PRRS and PCV2b VL were quantified using serum viremia data from 0 to 21 and 0 to 42 days post-infection, respectively. Bivariate single SNP genome-wide association studies (GWAS) were conducted fitting animal models in ASReml4, where ADG, PRRS VL, and PCV2b VL of vaccinated (Vx) and non-vaccinated (Non-Vx) pigs were analyzed as separate traits. For each GWAS, SNPs with –log₁₀ p-values greater than 2, 2.5, or 3 were used to assess statistical overrepresentation of neighboring genes associated with protein pathways using PANTHER software, and overrepresentation of health (production) QTL for VL (ADG) using a binomial test.

Regions near the major histocompatibility complex were associated with PCV2b VL and ADG Post Co-X of Vx and Non-Vx pigs (P<0.0001). For Vx pigs, additional regions on SSC11 and 12, and SSC1 and 7, were associated with ADG Pre and Post Co-X, respectively (P<0.00001). Regions on SSC15 were associated with ADG of Non-Vx pigs Pre and Post Co-X (P<0.00001). Genes near SNPs associated with ADG of Vx pigs Pre Co-X were overrepresented for cell signaling, and for chromatin organization/assembly for PCV2b VL of Vx pigs and ADG of Non-Vx pigs Pre and Post Co-X. For ADG of Vx pigs Post Co-X, production QTL and genes near neighboring SNPs were overrepresented for metabolic processes and macrophage activation.

Taken together, these results provide biological evidence that support statistical associations identified from GWAS, which present opportunities to select for improved host response to PRRSV and PCV2b co-infection. Research was supported by USDA-NIFA grants 2012-38420-19286 and 2013-68004-20362.