Probing Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Infection Control Mechanisms using Differential Gene Expression

Porcine reproductive and respiratory syndrome (PRRS) is economically the most important disease of pigs with annual U.S. losses of $664M. Understanding transcriptional control of anti-viral responses should reveal mechanisms to help control PRRS. The PRRS Host Genetics Consortium (PHGC) was established to combine efforts of scientists from university, government and commercial pig genetics and animal health companies to assess the role of genetics in determining pig resistance/susceptibility to PRRS virus (PRRSV) infection, pathology and growth effects. The PHGC used a nursery pig PRRSV infection model with deep sampling for phenotypic analyses, extensive genotyping (60K SNPchip) and a shared database http://www.animalgenome.org/lunney/. To address disease resistance mechanisms we probed the blood transcriptome of PHGC pigs using RNAseq. Based on data from 14 trials using ~200 PRRSV-infected pigs each we identified a genomic region on SSC4, and a putative candidate gene GBP5, which had significant impact on variation in viral load and growth responses following challenge with each of 2 different PRRSV isolates. Using RNAseq analyses we have identified genes that are differentially expressed in PRRS resistant versus susceptible pigs. Our current efforts are aimed at probing for alternate control and regulatory networks by comparing pigs with differential PRRSV responses as well as assessing interactions between viral and host genes. This data has already enabled us to identify expression QTL (eQTL) and should reveal new pathways that may be used for design of novel vaccines and biotherapeutics. Support: US National Pork Board, USDA ARS and NIFA, Genome Canada, Genome Alberta, pig breeding companies.