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ARS Home » Northeast Area » Beltsville, Maryland (BARC) » Beltsville Agricultural Research Center » Animal Parasitic Diseases Laboratory » Research » Publications at this Location » Publication #326310

Research Project: FUNCTIONAL GENOMIC APPROACHES FOR CONTROLLING DISEASES OF SWINE

Location: Animal Parasitic Diseases Laboratory

Title: Differences in Whole Blood Gene Expression Associated With Infection Time-course and Extent of Fetal Mortality in a Reproductive Model of type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Infection

Author
item WILKINSON, JAMIE - University Of Alberta
item LADINIG, ANDREA - University Of Veterinary Medicine
item BAO, HUA - University Of Alberta
item KOMMADATH, ARUN - University Of Alberta
item STOTHARD, PAUL - University Of Alberta
item Lunney, Joan
item HARDING, JOHN - University Of Saskatchewan
item PLASTOW, GRAHAM - University Of Alberta

Submitted to: PLoS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/19/2016
Publication Date: 4/16/2016
Citation: Wilkinson, J., Ladinig, A., Bao, H., Kommadath, A., Stothard, P., Lunney, J.K., Harding, J.C., Plastow, G.S. 2016. Differences in Whole Blood Gene Expression Associated With Infection Time-course and Extent of Fetal Mortality in a Reproductive Model of type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Infection. PLoS One. 11(4):e0153615.

Interpretive Summary: Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection of pregnant females (gilts) causes fetal death and increased piglet mortality, but there is substantial variation in the extent of reproductive pathology between individual dams. For this study we characterized the pregnant gilt whole blood transcriptional response to type 2 PRRSV infection. We asked whether we could identify gene expression signatures associated with gilts that had litters with low or high fetal mortality rates at necropsy, 21 days post-PRRSV inoculation (dpi). At 2 dpi all gilts exhibited an upregulation of genes involved in innate immunity with a concomitant decrease in T lymphocyte marker expression; by 6 dpi the pattern had reversed. Importantly, the gilts with low fetal mortality exhibited a higher baseline (pre-infection) expression of interferon-stimulated and pro-inflammatory genes prior to infection, and of T cell markers at 2 dpi. This indicated that these gilts had a rapid development of their immune response to PRRSV infection. These results could ultimately result in the development of a biomarker panel that could be used to predict PRRSV-associated reproductive pathology.

Technical Abstract: Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection of pregnant females causes fetal death and increased piglet mortality, but there is substantial variation in the extent of reproductive pathology between individual dams. This study used RNA-sequencing to characterize the whole blood transcriptional response to type 2 PRRS in pregnant gilts during the first week of infection (at 0, 2, and 6 days post-inoculation), and attempted to identify gene expression signatures associated with a low or high level of fetal mortality rates (LFM and HFM; n=8/group) at necropsy, 21 days post-inoculation. The initial response to infection measured at day 2 saw an upregulation of genes involved in innate immunity, such as interferon-stimulated antiviral genes and inflammatory markers, and apoptosis. A concomitant decrease in expression of protein synthesis and T lymphocyte markers was observed. By day 6 the pattern had reversed, with a drop in innate immune signaling and an increase in the expression of genes involved in cell division and T cell signaling. Differentially expressed genes (DEGs) associated with extremes of litter mortality rate were identified at all three time-points. Among the 15 DEGs upregulated in LFM gilts on all three days were several genes involved in platelet function, including integrins ITGA2B and ITGB3, and the chemokine PF4 (CXCL4). LFM gilts exhibited a higher baseline expression of interferon-stimulated and pro-inflammatory genes prior to infection, and of T cell markers two days post-infection, indicative of a more rapid progression of the immune response to PRRSV. This study has increased our knowledge of the early response to PRRSV in the blood of pregnant gilts, and could ultimately lead to the development of a biomarker panel that can be used to predict PRRSV-associated reproductive pathology.