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ARS Home » Northeast Area » Beltsville, Maryland (BARC) » Beltsville Agricultural Research Center » Animal Parasitic Diseases Laboratory » Research » Research Project #431901

Research Project: Evaluation of Swine Immunity and Development of Novel Immune and Genomic Intervention Strategies to Prevent and/or Treat Respiratory Diseases of Swine

Location: Animal Parasitic Diseases Laboratory

2017 Annual Report

4. Accomplishments
1. Discovery of genetic variants that characterize pigs with superior responses to viral infection or vaccination. ARS scientists in Beltsville, Maryland, partnered with Iowa State and Kansas State University researchers to work on the most economically important disease of pigs, porcine reproductive and respiratory syndrome (PRRS). Our goal was to identify genetic markers of pigs that respond especially well to vaccination against PRRS and that thrive in the face of co-infection with PRRS virus and a second virus of major concern, the porcine circovirus. Specific regions in the pig genome were identified that resulted in improved weight gain while controlling viral load (level of virus in the bloodstream) of commercial crossbred nursery pigs. Based on these results pig breeders will be able to select for more disease-resistant pigs, improving the health of swine and reducing economic losses attributable to viral infection.

2. Genomics helps predict a pig’s resistance to respiratory viral infections. Porcine Reproductive and Respiratory Syndrome (PRRS) is a devastating disease for the swine industry, causing $600 million in losses/year for U.S. pork producers. ARS scientists in Beltsville, Maryland partnered with researchers at Iowa State and Kansas State Universities to investigate whether they could accurately predict genes that control both PRRS virus (PRRSV) load, i.e., level of virus in the bloodstream, and weight gain. To do this PRRS resistance prediction they set up statistical groups (training and validation datasets) from pig populations with different genetic backgrounds that had been infected with two different PRRSV isolates; further, to improve the accuracy of their predictions, sets of genetic markers from across the whole genome were used as genetic tags. The response of individual pigs to PRRSV infection was predicted by these data with moderate accuracy with limited influence due to PRRSV isolate. This PRRS resistance prediction tool will aid pig breeders in improving the health of the swine herd, and reduce losses associated with these infections.

3. Certain pigs better tolerate viral burdens. Pig responses to viral infection were probed to answer the question: Does an animal survive an infection due to resistance (reduced level of virus in the bloodstream) and/or due to tolerance (lower impact of virus infection on performance, e.g. weight gain, meat quality)? This is quite important for Porcine Reproductive and Respiratory Syndrome virus (PRRSV) infections since they are economically a devastating disease for the swine industry; therefore, ARS scientists in Beltsville, Maryland, partnered with others at Iowa State University, Kansas State University and the Roslin Institute in Scotland to develop a mathematical model describing serum PRRSV responses. Our past work has provided evidence in support of a genetic basis for PRRS resistance but it was not known whether pigs also differed genetically in PRRS tolerance. Evidence for genetic variation in tolerance of pigs to PRRS was weak when based on data from only PRRSV infected piglets. However, simulations indicated that differences in genetic background may impact tolerance and this could be detected if comparable data on uninfected relatives were available. We concluded that unlike the proven genetics of resistance to PRRS virus infection, genetics of tolerance can be predicted but will be more difficult to verify.

4. Susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV) infection has a heritable component, yet little is known about the underlying causes. The PRRS Host Genetics Consortium of researchers from ARS in Beltsville, Maryland, Iowa State University, the University of Alberta and PigGen Canada explored how different pigs responded to viral infection. We performed complex analyses, integrating pig genotypes, blood cell gene expression and post infection phenotypes (viral load and weight gain) over 42 days to reveal differences, termed quantitative trait loci, for 560 PRRSV-responsive genes. These studies revealed that several immune-related pathways including cytokine signaling, interferon signaling and antigen presentation were important and contribute to poor responses (higher viral load or lower weight gain) after PRRSV infection. As a result of this effort, we expect to provide breeders and producers information on selecting pigs with superior anti-PRRS responses and increased resistance to swine respiratory infections.

5. PRRS virus induces pathology in fetuses as well as at the uterine maternal-fetal attachment site. Porcine reproductive and respiratory syndrome virus (PRRSV) infections during pregnancy cause U.S. producers losses of over $300 million annually. ARS scientists at Beltsville, Maryland, the University of Saskatchewan and the University of Alberta, probed maternal and fetal factors that could be predictive of PRRS severity and resilience in newborn piglets. Fetal death and high viral load clustered in litters suggesting viral transmission between fetuses starting from a few index fetuses in each litter, with large fetuses at greater risk; also, gene expression profiles indicated an active, adaptive immune response to the viral infection with both antibody and cell-mediated immune components in the sow; in contrast, the fetus exhibited an immature, innate and inflammatory immune response with up-regulation of genes implicated in infectious disease pathology. Sows with higher viral load and lower T cell immune signaling were more likely to have virus infected fetuses. Thus, fetal pathology is influenced by events occurring at both the maternal-fetal attachment site as well as within the PRRSV-infected fetus. Efforts are underway to improve reproductive PRRS control methods.

6. In the fight against human tuberculosis, piglets prove an excellent research model. Numerous groups have attempted to develop vaccines to control human tuberculosis (TB) andto date the only vaccine available against TB is Bacillus Calmette-Guerin (BCG), however, there have been major failures in the development of new pediatric vaccines against TB due to incomplete knowledge of the immune response elicited in the neonate after vaccination. Since the pig is known to have an immune system similar to humans, ARS scientists at Beltsville, Maryland, worked with researchers at Colorado State University to determine if piglets become infected with TB and have similar immunological responses to those found in infants vaccinated with BCG. Both vaccinated and non-vaccinated pigs were challenged via the aerosol route with Mycobacterium tuberculosis (Mtb). As compared to human infants, neonatal pigs demonstrated a similar course of TB infection as well as similar immune response to BCG and to TB challenge. Overall, our results affirmed that the pig should be a good model for the human neonate for development of diagnostics, drugs and vaccines against TB.

7. New tools for studying swine immunology. Analyses of disease and vaccine responses require sophisticated immune tools yet those for pigs are limited. ARS scientists at Beltsville, Maryland, worked with commercial partners and researchers at Ohio State and Kansas State Universities and the University of Bristol, U.K., to address this issue, supported in part by a USDA U.S.-U.K. collaboration grant. Numerous swine immune proteins (cytokines, chemokines) were expressed and used for immunizations to develop specific reagents [monoclonal antibodies (mAbs)] reactive with these proteins. Panels of mAbs reactive with swine immune proteins, interleukin-6 (IL-6), IL-13, IL-17A, interferon-beta (IFNb) and IFNg, have now been produced. Tools and reagents generated by this project will be made available for swine immune, disease and biomedical research efforts worldwide.

Review Publications
Tuggle, C.K., Giuffra, E., White, S.N., Clarke, L., Zhou, H., Ross, P.J., Acloque, H., Reecy, J.M., Archibald, A., Boichard, M., Chamberlain, A., Cheng, H.H., Crooijmans, R., Delany, M., Groenen, M.A., Hayes, B., Lunney, J.K., Plastow, G.S., Silverstein, J., Song, J., Watson, M. 2016. GO-FAANG meeting: A gathering on functional annotation of animal genomes. Animal Genetics. 47(5):528-533.

Waide, E.H., Tuggle, C.K., Serao, N., Schroyen, M., Hess, A., Rowland, R., Lunney, J.K., Plastow, G., Dekkers, J. 2017. Genome-wide association analyses of piglet responses to infection with two porcine reproductive and respiratory syndrome virus isolates. Journal of Animal Sciences. 95:16-38.

Hay, E.A., Choi, I., Xu, L., Zhou, Y., Rowland, R., Lunney, J.K., Liu, G. 2017. CNV analysis of host responses to porcine reproductive and respiratory syndrome virus infection. Journal of Genomics. 5:58-63.

Dunkelberger, J., Serao, N., Neiderwerder, M., Kerrigan, M., Lunney, J.K., Rowland, R., Dekkers, J. 2017. Effect of a major QTL for PRRS-resistance on response to co-infection with PRRS and PCV2b in commercial pigs, with or without prior vaccination for PRRS. Journal of Animal Science. 95:584-598.

Lough, G., Rashidi, H., Kyriazakis, I., Dekkers, J.C., Hess, A.S., Hess, M.K., Deeb, N., Kause, A., Lunney, J.K., Rowland, R.R., Mulder, H., Doeschl-Wilson, A. 2017. Using multi-trait and random regression models to identify genetic variation in tolerance of pigs to Porcine Reproductive and Respiratory Syndrome virus. Genetics Selection Evolution. 49:37.

Kommadath, A., Bao, H., Choi, I., Reecy, J.M., Koltes, J.E., Fritz-Waters, E., Eisley, C.J., Grant, J.R., Rowland, R.R., Tuggle, C.K., Dekkers, J.C., Lunney, J.K., Guan, L., Stothard, P., Plastow, G.S. 2017. Genetic architecture of gene expression underlying variation in susceptibility to porcine reproductive and respiratory syndrome virus infection. Scientific Reports. 7:46203. doi:10.1038/srep46203.

Harding, J., Ladininig, A., Novakovic, P., Detmer, S., Wilkinson, J., Yang, T., Lunney, J.K., Plastow, G. 2017. Novel insights into host responses and the reproductive pathophysiology of type 2 porcine reproductive and respiratory syndrome (PRRS). Veterinary Microbiology. 209: 114-123. 10.1016/j.vetmic.2017.02.019.

Dekkers, J., Rowland, R., Lunney, J.K., Plastow, G. 2017. The use of host genetics to control porcine reproductive and respiratory syndrome. Veterinary Microbiology. S0378-1135(16)30678-2. doi: 10.1016/j.vetmic.2017.03.026.