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Genome-wide analysis of thetranscriptional response to porcinereproductive and respiratory syndromevirus infection at the maternal/fetalinterface and in the fetus

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  • Background:Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection of pregnant pigs can result incongenital infection and ultimately fetal death. Little is known about immune responses to infection at thematernal-fetal interface and in the fetus itself, or the molecular events behind virus transmission and diseaseprogression in the fetus. To investigate these processes, RNA-sequencing of two sites, uterine endothelium withadherent placental tissue and fetal thymus, was performed 21 days post-challenge on four groups of fetusesselected from a large PRRSV challenge experiment of pregnant gilts: control (CON), uninfected (UNINF), infected(INF), and meconium-stained (MEC) (n = 12/group). Transcriptional analyses consisted of multiple contrasts betweengroups using two approaches: differential gene expression analysis and weighted gene co-expression networkanalysis (WGCNA). Biological functions, pathways, and regulators enriched for differentially expressed genes ormodule members were identified through functional annotation analyses. Expression data were validated byreverse transcription quantitative polymerase chain reaction (RTqPCR) carried out for 16 genes of interest.Results:The immune response to infection in endometrium was mainly adaptive in nature, with the mostupregulated genes functioning in either humoral or cell-mediated immunity. In contrast, the expression profile ofinfected fetal thymus revealed a predominantly innate immune response to infection, featuring the upregulation ofgenes regulated by type I interferon and pro-inflammatory cytokines. Fetal infection was associated with an increase inviral load coupled with a reduction in T cell signaling in the endometrium that could be due to PRRSV-controlledapoptosis of uninfected bystander cells. There was also evidence for a reduction in TWIST1 activity, a transcriptionfactor involved in placental implantation and maturation, which could facilitate virus transmission or fetal pathologythrough dysregulation of placental function. Finally, results suggested that events within the fetus could also drive fetalpathology. Thymus samples of meconium-stained fetuses exhibited an increase in the expression of pro-inflammatorycytokine and granulocyte genes previously implicated in swine infectious disease pathology.Conclusions:This study identified major differences in the response to PRRSV infection in the uterine endometriumand fetus at the gene expression level, and provides insight into the molecular basis of virus transmission and diseaseprogression.

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    Attribution-NonCommercial 4.0 International
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    • Wilkinson, J. M. ( 1 ), Bao, H. ( 1 ), Stothard, P. ( 1 ), Plastow, G. S. ( 1 ), Ladinig, A. ( 2,3 ), Harding, J. C. S. ( 3 ), Hong, L. ( 4,5 ), & Lunney, J. K. ( 4 ). (n.d.). Genome-wide analysis of the transcriptional response to porcine reproductive and respiratory syndrome virus infection at the maternal/fetal interface and in the fetus. BMC Genomics, 17(1).