It is estimated that porcine reproductive and respiratory syndrome virus costs U.S. hog producers $640 million, with an additional $360 million in annual veterinary costs, making it the most significant disease facing today’s industry. Vaccines, biosecurity measures and proposed methods for eradication have had limited success.
The aim of the PRRS Host Genetics Consortium is to identify genomic markers and pathways associated with host response to PRRSV infection. These markers could potentially be used for genetic selection of pigs for increased resistance or reduced susceptibility to the virus.
Swine responses to PRRSV infection differ substantially, and the PHGC’s aim is to assess the role of genetics in determining pig resistance and susceptibility to PRRSV infection, and related pathology and growth effects. As a result of the first phase of the PHGC, a genetic marker, or quantitative trait locus, was identified; it maps to swine chromosome 4 (SSC4) and accounts for 15% of genetic differences between pigs in viral load and 11% of genetic differences in weight gain after PRRSV infection.
Further efforts by the PHGC team affirmed that the SSC4 gene is guanylate binding protein 5 (GBP5), as reported in the Pork Checkoff Report Magazine Fall 2015. However, there was a limitation on these results — they affirmed genetic control to only one PRRSV isolate, NVSL97.
Broad team approach
This year a major Genome Canada-funded project, led by the University of Alberta, was completed. It funded a new set of five PHGC infection trials using a more recent PRRSV isolate, KS-2006-72109 (KS06).
Weaned commercial pigs, provided by PigGen Canada breeders, were infected at Kansas State University and followed for approximately 42 days post-infection. After detailed viral response phenotyping and genomic DNA genotyping, genome-wide association analyses were performed at Iowa State University.
The GWAS results affirmed that the gene on SSC4 showed comparable significant effects on viral load, but lower effects on weight gain, when results from pigs infected with KS06 were compared to earlier trials with the NVSL97 virus. These results could have a major impact in the swine industry by enabling geneticists to develop plans for marker-assisted selection of pigs with improved response to PRRSV.
Importantly, adding to funds from the National Pork Board and USDA-National Institute of Food and Agriculture that were used for the first set of PHGC trials, the Genome Canada funds enabled PHGC researchers to perform further detailed analyses of anti-PRRSV infection responses. Using the extensive PRRS sample repository, PHGC researchers have also probed disease resistance mechanisms by evaluating serum protein expression (antibody and cytokine) and whole-blood gene expression profiles. These analyses have identified critical immune proteins and genes that are differentially expressed in response to PRRSV infection, as well as novel broadly neutralizing antibodies. As a result, alternate PRRS control and regulatory networks can now be explored for help in developing new vaccines and biotherapeutics.
Stage set for targeting genes
Infection with PRRSV elicits a weak immune response that is not fully protective and results in persistent infection in a subset of pigs. The PHGC studies have begun to identify genetic markers that are predictive for pigs that clear PRRSV faster and grow better. This sets the stage for targeting these genetic regions to identify the mechanisms that induce the early anti-PRRSV response.
Despite substantial research efforts, the exact components of a protective anti-PRRSV immune response are still not known. The detailed PRRS response analyses funded by Genome Canada and USDA-NIFA grants may lead to new anti-PRRSV biotherapeutics or vaccines.
In the past, genetic experiments involved the study of a limited number of animals using a limited number of assays. By collecting detailed data on large numbers of PRRSV-infected pigs and related samples, PHGC researchers have been able to verify important genotypes and phenotypes that predict resistance, tolerance or susceptibility to PRRSV infection.