Opportunities for genetic selection for resistance to PRRS infection in pigs in Belgium (PigRReSist1)

The objectives of the project are:

1. Examine the susceptibility/resistance of macrophages of Piétrain, Duroc, Landrace and Large White boars against PRRS field viruses (LV, Flanders 13) and PRRS attenuated vaccine virus by (i) collecting blood from pigs of the different pig breeds, (ii) isolating and differentiating blood monocytes and (iii) determining their susceptibility upon inoculation with PRRSV1-LV, PRRSV1-Flanders 13, PRRSV2-VR2332 and PRRSV1 vaccine strain DV (MSD).
2. Identify the genetic correlates with PRRSV susceptibility/resistance. This will be done by two approaches. With a candidate gene approach, the cDNA of different cellular entry mediators (Siglec-1, Siglec-10, DC-SIGN, receptor x, CD163, proteases) will be sequenced and compared between the different breeds. Certain mutations may lead to different susceptibilities. In parallel, a more general genetic approach will be used. A genome wide association study (GWAS) will be performed on the different breeds using the GGP Porcine 50k SNP array with the macrophage susceptibility test described above as phenotype. Next whole genome sequencing will be performed on a limited number of extremes: highly susceptible pigs versus resistant/low susceptible pigs. Upon identification of certain genes or regulatory sequences, we will confirm their role in susceptibility/resistance in vitro and in vivo. For the in vitro work, macrophages of resistant pigs will be transformed in susceptible cells by transfection with RNA encoding the protein that is associated with susceptibility. For the in vivo work, selected ‘resistant’ and ‘susceptible’ pigs will be challenged with wild type PRRSV and the viremia and serological response will be followed. For each identified gene, a genetic test will be developed in order to classify pigs into ‘resistant’ and ‘susceptible’ animals.
3. Examine if the immune response is genetically determined based on the responsiveness of pigs after vaccination. For the latter aim, material will be collected from multivaccinated sows. SNP analysis and WGS will be performed on two groups of pigs: animals with a high immunological response and animals with a low immune response. Finally, high-responding and low-responding pigs will be vaccinated and challenged with wild type PRRSV.