Genetics of host responses to infection with porcine reproductive and respiratory syndrome virus (PRRSV)

More than 20 years after its emergence, the viral disease porcine reproductive and respiratory syndrome (PRRS) is still having major impacts on pig health and welfare. PRRS results in reproductive failure and respiratory disorders. Since the early 1990s, vaccine therapy and management practices strategies have had a limited impact on the spread of the disease. PRRS remains a challenge to the sustainability of pig production, especially with the emergence of new highly pathogenic PRRSV strains. A potentially sustainable solution to the problem of PRRS lies in breeding animals for increased resistance, most likely in combination with other control measures. This is possible, in principle, as we have previously demonstrated the presence of genetic variation in PRRS disease outcomes, and in transcriptional responses to infection in an in vitro challenge model. Current resources include DNA, 60k SNP genotypes and phenotypic data from a population of 1000+ sows exposed to a PRRS outbreak, an in vitro challenge model system, and access to independent genetic studies on PRRS resistance. This project will exploit all available information to gain insight into the genetic control of PRRS resistance or tolerance, to identify loci implicated in between-host variation in resistance to PRRSv infections and in disease outcomes in PRRS-affected herds, and to devise strategies to exploit this information in breeding programs. The specific objectives are: 1. TO QUANTIFY THE GENETIC CONTROL OF PRRS RESISTANCE OR TOLERANCE IN SOWS USING 60K SNP ARRAY DATA We have shown that the numbers of dead and mummified piglets following a PRRS outbreak is heritable. Further, analyses of a low-density SNP chip has indicated some, albeit imprecise, regions of the genome where PRRS-resistance or PRRS-tolerance loci are likely to reside. Data from a 60k SNP array is now available for these sows, and will be highly informative for elucidating the host genetic control of PRRS resistance. The student analyse these data to determine the location of the loci contributing to PRRS resistance in reproductive sows, and test whether these loci interact with sow genetic background or age. 2. TO PERFORM META-ANALYSIS OF SNP ARRAY GENOTYPE DATA FOR PRRS RESISTANCE We have access to results of SNP array data for PRRS resistance in growing pigs, collected in a separate population under different environmental conditions. We will perform a meta-analysis of the two sets of results. This will determine loci that show generic importance across datasets (with differing trait definition and environment conditions) and distinguish these from loci that are dataset specific. 3. TO CONTRAST RESULTS FROM IN VIVO AND IN VITRO STUDIES OF PRRS RESISTANCE The datasets described above describe in vivo outcomes of infection and disease. From a genetic control perspective it is the early response to the host to infection, particularly innate responses, that are most likely to contribute to effective disease control in the field. The student will analyse outcomes of our in vitro challenge models, and contrast these with the results obtained from the field disease data. Comparison of the results will refine the loci that are most likely to be of practical utility for disease control. 4. TO DETERMINE THE FEASIBILITY OF BREEDING PIGS FOR ENHANCED PRRS-RESISTANCE Using the data above, the student will explore the feasibility of including PRRS resistance into practical breeding programs at Genus. To avoid the need for exposing animals to infection it will be necessary to use SNP genotypes (identified above) to achieve this. The student will: (i) devise strategies for best including these data into ongoing selection programs, (ii) estimate the likely impact such a breeding strategy on disease and performance outcomes should a PRRS-outbreak occur, and (iii) estimate the net impact of this approach on the breeding program as a whole.