Investigating Susceptibility to PRRS in the Pregnant Gilt and Fetus Using Transcriptomics

Improving genetic resistance to porcine reproductive and respiratory syndrome (PRRS), or identifying therapeutic targets, will require a greater understanding of the molecular mechanisms that govern differences in disease susceptibility between animals. Samples have been collected for transcriptomic analysis of a ‘Pregnant gilt model’ of PRRS virus infection. Gilts were inoculated (n = 115) or sham-inoculated (n = 19) during the final trimester of gestation. Whole blood and peripheral blood mononuclear cells (PBMC) for RNA isolation were collected at the following infection time-points: Day 0, 2, 6, and 19. At necropsy, additional samples were taken from gilt respiratory and reproductive tissues, and from individual fetuses. Measures of viral load in gilt sera and fetuses, and the extent of fetal pathology, will be used to classify animals into susceptibility groups. Preliminary results clearly indicate that differences in susceptibility do exist within the model. Transcriptomic experiments will use a combination of porcine microarrays, RNAseq and qPCR to address the following objectives: 1) Identify biomarkers for susceptibility in pregnant gilts [incorporating a comparison of animals with favorable and non-favorable genotypes at the recently identified region on SSC4 associated with resistance to PRRS (PPRS Host Genetics Consortium, PHGC)]; 2) Compare host response to infection in pregnant gilts with that of PHGC growing pigs; 3) Identify biomarkers for in vitro responsiveness of PBMC to mitogen and PRRSV and determine whether they correlate with susceptibility status; and 4) Investigate PRRSV infection in the fetus and uterus/placenta with regard to pathology, resistance, and virus transmission.  Funding: Genome Canada.