Effect of the host genotype at a Porcine Reproductive and Respiratory Syndrome (PRRS) resistance marker on evolution of the modified-live PRRS vaccine virus in pigs

Authors: ROWLAND, RAYMOND - University Of Illinois; DOERKSEN, TYLER - Kansas State University; LU, ANDREA - Kansas State University; SHEAHAN, MAUREEN - Kansas State University; Lunney, Joan; DEKKERS, JACK - Iowa State University; PALINSKI, RACHEL - Kansas State University

Submitted to: Virus Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/10/2022
Publication Date: 5/11/2022
Citation: Rowland, R.R., Doerksen, T., Lu, A., Sheahan, M., Lunney, J.K., Dekkers, J., Palinski, R.M. 2022. Effect of the host genotype at a Porcine Reproductive and Respiratory Syndrome (PRRS) resistance marker on evolution of the modified-live PRRS vaccine virus in pigs. Virus Research. https://doi.org/10.1016/j.virusres.2022.198809.
DOI: https://doi.org/10.1016/j.virusres.2022.198809

Interpretive Summary: Porcine Reproductive and Respiratory syndrome virus (PRRSV) causes economically impactful disease for US and global swine producers. A specific host genome polymorphism, a genetic allele “B” of WUR, was found to be associated with lowered viral load and improved weight gain in PRRSV infected nursery pigs. For infection control the industry uses modified-live virus vaccines. This manuscript determined the effect of the B PRRS resistance allele on viral diversity after vaccination; sera from B allele pigs had more variable viral genome sequences when compared to AA genotype pigs whose serum lacked viral genome variability. This difference in viral diversity might be due to the earlier initiation, and potentially broader, immune response by B pigs. If correct this difference has impact on future vaccine design.

Technical Abstract: Porcine Reproductive and Respiratory syndrome (PRRS), caused by the PRRS virus (PRRSV), is one of the most economically impactful diseases to US and global swine producers. Protective efficacy of the primary means of PRRS control, i.e., modified-live virus (MLV) vaccines, is however, largely associated with genetically similar, or homologous, strains and to a much lesser extent with genetically dissimilar, or heterologous strains. The single nucleotide polymorphism (SNP) WUR10000125 on Sus scrofa chromosome 4 has been shown to account for 16% of the genetic variance in viral load and 11% of the genetic variance in weight gain in nursery pigs following PRRSV infection. In a previous study, pigs with either the favorable (AB and BB) or unfavorable (AA) genotype at this SNP were monitored for viral load by qRT-PCR on 7, 14, and 26 days post vaccination (dpv) with a ResPRRSV MLV. From this study, samples from 8 pigs were selected for PRRSV whole genome sequencing and bioinformatics analysis of consensus and subconsensus variants of the PRRSV. PRRSV consensus genomes were used to develop a host-genotype driven evolutionary model. Subconsensus variants were used to identify differential variant populations between host-associated PRRSV quasispecies. This resulted in a model that accurately predicted host WUR genotype from PRRSV consensus sequences and provided insight into the consensus-level changes that were associated with host-genotype at this SNP. The PRRSV consensus genomes carried by pigs with the AB/BB genotype were more variable (and vaccine-like) at 7 dpv compared to the PRRSV genomes carried by pigs with the AA genotype, which lacked any group-membership variability. These results suggest that the AB/BB genotype animals are more likely to develop a broader immune response than AA animals. Furthermore, subconsensus PRRSV population analysis revealed significant differences in vaccine quasispecies size between samples from genotype AA (limited population) and AB/BB (large population) animals. The results of this study can be used to improve available PRRSV vaccines by characterizing the host-driven changes following vaccination.