Whole Blood Microarray Analysis of Pigs Showing Extreme Phenotypes After a Porcine Reproductive and Respiratory Syndrome Virus (PRRSv) Infection

As part of the PRRS host genetics consortium (PHGC), 100 animals with extremely different growth rates and viremia levels after a PRRS virus (PRRSv) infection were selected in order to find underlying molecular differences in susceptible versus resistant pigs. A microarray experiment was conducted on whole blood RNA samples taken at 0, 4 and 7 days post infection (dpi). Factors examined were weight gain, viral load and effect of SSC4 WUR10000125 (WUR) genotype, which is associated with a significant portion of the genetic variability in response to PRRS.

Little information could be obtained through differential expression (DE) analysis that contrasted pigs with extreme phenotypes for growth or viral load. However, several interesting clusters of genes have been identified when applying Weighted Gene Co-expression Network Analysis (WGCNA) to these datasets. On 4dpi compared to 0dpi, a module containing numerous immune response genes (cytokines, chemokines, interferon type I stimulated genes, apoptotic genes and genes regulating complement activation), was found to be correlated with weight gain (p=0.03) and WUR genotype (p=0.04). On 7dpi compared to 0dpi, an adaptive immune response module was correlated with weight gain (p=0.09) and WUR genotype (p=0.07). In addition, Partial Correlation and Information Theory (PCIT) analyses found differentially wired hub genes that could explain some of these findings. We conclude that there are molecular differences between pigs with extreme phenotypes in response to PRRSv infection, though they can be difficult to discover with conventional DE expression analyses. Co-expression analyses can be used to reveal those network differences.