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. 2016 Apr 19;11(4):e0153615. doi: 10.1371/journal.pone.0153615. eCollection 2016.


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 PRRSV 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 2 days post-inoculation 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Cells / immunology
  • Blood Cells / virology*
  • Female
  • Fetal Death
  • Fetal Mortality
  • Gene Expression / genetics*
  • Immunity, Innate / immunology
  • Porcine Reproductive and Respiratory Syndrome / genetics*
  • Porcine Reproductive and Respiratory Syndrome / immunology
  • Porcine Reproductive and Respiratory Syndrome / mortality*
  • Porcine respiratory and reproductive syndrome virus / immunology
  • Pregnancy
  • Pregnancy Complications, Infectious / genetics
  • Pregnancy Complications, Infectious / immunology
  • Pregnancy Complications, Infectious / mortality
  • Reproduction / genetics*
  • Reproduction / immunology
  • Swine / immunology
  • Swine / virology*
  • T-Lymphocytes / immunology

Grants and funding

This work was funded by grants from Genome Canada (genomecanada.ca) and Genome Prairie (genomeprairie.ca) to support the following project: "Application of Genomics to Improve Swine Health and Welfare". Administrative support was provided by Genome Alberta (genomealberta.ca). HB and PS are grateful for financial support from the Alberta Livestock and Meat Agency (alma.alberta.ca) and Alberta Innovates – Bio Solutions (bio.albertainnovates.ca), respectively. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.