Differences in Whole Blood Gene ExpressionAssociated with Infection Time-Course andExtent of Fetal Mortality in a ReproductiveModel of Type 2 Porcine Reproductive andRespiratory Syndrome Virus (PRRSV)Infection

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Wilkinson JM, Ladinig A, Bao H,Kommadath A, Stothard P, Lunney JK, et al. (2016)Differences in Whole Blood Gene ExpressionAssociated with Infection Time-Course and Extent ofFetal Mortality in a Reproductive Model of Type 2Porcine Reproductive and Respiratory SyndromeVirus (PRRSV) Infection. PLoS ONE 11(4):e0153615. doi:10.1371/journal.pone.0153615

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Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection of pregnantfemales causes fetal death and increased piglet mortality, but there is substantial variationin the extent of reproductive pathology between individual dams. This study used RNA-sequencing to characterize the whole blood transcriptional response to type 2 PRRSV inpregnant gilts during the first week of infection (at 0, 2, and 6 days post-inoculation), andattempted to identify gene expression signatures associated with a low or high level of fetalmortality rates (LFM and HFM; n = 8/group) at necropsy, 21 days post-inoculation. The ini-tial response to infection measured at 2 days post-inoculation saw an upregulation of genesinvolved in innate immunity, such as interferon-stimulated antiviral genes and inflammatorymarkers, and apoptosis. A concomitant decrease in expression of protein synthesis and Tlymphocyte markers was observed. By day 6 the pattern had reversed, with a drop in innateimmune signaling and an increase in the expression of genes involved in cell division and Tcell signaling. Differentially expressed genes (DEGs) associated with extremes of litter mor-tality rate were identified at all three time-points. Among the 15 DEGs upregulated in LFMgilts on all three days were several genes involved in platelet function, including integrinsITGA2BandITGB3, and the chemokinePF4 (CXCL4). LFM gilts exhibited a higher baselineexpression of interferon-stimulated and pro-inflammatory genes prior to infection, and of Tcell markers two days post-infection, indicative of a more rapid progression of the immuneresponse 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 bio-marker panel that can be used to predict PRRSV-associated reproductive pathology.

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http://purl.org/coar/resource_type/c_6501 http://purl.org/coar/version/c_970fb48d4fbd8a85

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