Limits...
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.

Wilkinson JM, Ladinig A, Bao H, Kommadath A, Stothard P, Lunney JK, Harding JC, Plastow GS - PLoS ONE (2016)

Bottom Line: A concomitant decrease in expression of protein synthesis and T lymphocyte markers was observed.Differentially expressed genes (DEGs) associated with extremes of litter mortality rate were identified at all three time-points.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, AB, Canada.

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 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.

No MeSH data available.


Related in: MedlinePlus

Interferon Signaling in Gilt Blood following PRRSV Infection.Type I and II interferon signaling pathways from Ingenuity Pathway Analysis. Genes whose expression is upregulated (red) at D2 compared to D0 (A) were also found to be downregulated (green) at D6 compared to D2 (B). Color intensity indicates magnitude of differential expression.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4836665&req=5

pone.0153615.g001: Interferon Signaling in Gilt Blood following PRRSV Infection.Type I and II interferon signaling pathways from Ingenuity Pathway Analysis. Genes whose expression is upregulated (red) at D2 compared to D0 (A) were also found to be downregulated (green) at D6 compared to D2 (B). Color intensity indicates magnitude of differential expression.

Mentions: Interferon signaling was the most significant pathway upregulated at D2 compared to D0. It was also one of the most significant pathways to be downregulated at D6 compared to D2. Many of the DEGs that are activated by, or regulate interferon signaling, are common to type I and II signaling pathways but some genes that are specific to type I or type II signaling were also identified, an indication that both pathways are likely involved in the initial response to PRRSV inoculation. DEGs that are involved or regulated by type I (principally interferon alpha or beta) and/or type II (interferon gamma) interferon signaling, and map to the IPA pathways, include the transcription factors IRF1, IRF9, STAT1 and STAT2, other signal transduction enzymes (JAK2, SOCS1), and a variety of molecules that interfere with virus replication within the cell (IFIT1, IFITM1, MX1, and OAS1) (Fig 1).


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.

Wilkinson JM, Ladinig A, Bao H, Kommadath A, Stothard P, Lunney JK, Harding JC, Plastow GS - PLoS ONE (2016)

Interferon Signaling in Gilt Blood following PRRSV Infection.Type I and II interferon signaling pathways from Ingenuity Pathway Analysis. Genes whose expression is upregulated (red) at D2 compared to D0 (A) were also found to be downregulated (green) at D6 compared to D2 (B). Color intensity indicates magnitude of differential expression.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836665&req=5

pone.0153615.g001: Interferon Signaling in Gilt Blood following PRRSV Infection.Type I and II interferon signaling pathways from Ingenuity Pathway Analysis. Genes whose expression is upregulated (red) at D2 compared to D0 (A) were also found to be downregulated (green) at D6 compared to D2 (B). Color intensity indicates magnitude of differential expression.
Mentions: Interferon signaling was the most significant pathway upregulated at D2 compared to D0. It was also one of the most significant pathways to be downregulated at D6 compared to D2. Many of the DEGs that are activated by, or regulate interferon signaling, are common to type I and II signaling pathways but some genes that are specific to type I or type II signaling were also identified, an indication that both pathways are likely involved in the initial response to PRRSV inoculation. DEGs that are involved or regulated by type I (principally interferon alpha or beta) and/or type II (interferon gamma) interferon signaling, and map to the IPA pathways, include the transcription factors IRF1, IRF9, STAT1 and STAT2, other signal transduction enzymes (JAK2, SOCS1), and a variety of molecules that interfere with virus replication within the cell (IFIT1, IFITM1, MX1, and OAS1) (Fig 1).

Bottom Line: A concomitant decrease in expression of protein synthesis and T lymphocyte markers was observed.Differentially expressed genes (DEGs) associated with extremes of litter mortality rate were identified at all three time-points.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, AB, Canada.

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 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.

No MeSH data available.


Related in: MedlinePlus