ARS | Publication request: Identifying putative candidate genes and pathways involved in immune responses to porcine reproductive and respiratory syndrome virus (PRRSV) infection

Submitted to: Animal Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 2, 2011
Publication Date: N/A

Interpretive Summary: This manuscript is aimed at understanding the role of host genetics in resistance to porcine reproductive and respiratory syndrome virus (PRRSV) infection. It compares differences in gene expression between RNAs collected from lungs and bronchial lymph node (BLN) tissues of high (HR) and low (LR) PRRSV burden pigs. The goal was to assess critical parameters that are missing in the HR pigs that account for their higher PRRSV burden and lower growth rates compared to LR pigs. The swine protein-annotated long oligonucleotide microarray, the Pigoligoarray, was used for these analyses; it has been proven to have a wider coverage of pig genes than earlier arrays, particularly those involved in stress and disease responses. When the differentially expressed (DE) genes were statistically evaluated differences between HR and LR PRRSV existed (p< 0.01) for 392 genes from lung RNAs. These DE genes were then used with Ingenuity pathway analyses (IPA) software to determine which immune pathways were differentially stimulated or blocked in HR versus LR tissue RNAs. The top IPA canonical pathways included Acute Phase Response Signaling, Crosstalk between Dendritic Cells and Natural Killer Cells, and Tight Junction Signaling with numerous immune response genes determined as critical in these pathways. One mechanism, regulation of complement activation, may have been blocked in HR (PRRSV susceptible) pigs and accounted for the poor clearance of PRRSV by infected macrophages. Multiple inhibiting signals may have prevented effective immune responses in susceptible HR pigs, although some protective genes were up-regulated in these pigs. It is likely that in HR pigs expression of genes associated with protection was delayed, so that the immune response was not stimulated early; thus PRRSV infection had prevented protective immune responses. This research will help animal health companies identify new targets for their anti-PRRS drug and vaccine approaches.

Technical Abstract: Differences in gene expression were compared between RNAs from lungs of high (HR) and low (LR) PRRSV burden pigs using the swine protein-annotated long oligonucleotide microarray, the Pigoligoarray. Pathway analyses were carried out to determine biological processes, pathways and networks that differ between the LR and HR responses. Differences between HR and LR pigs for 16 signaling pathways existed [p<0.01/-log(p-value)›1.96]. Top canonical pathways included Acute Phase Response Signaling, Crosstalk between Dendritic Cells and Natural Killer Cells, and Tight Junction Signaling with numerous immune response genes that were up-regulated (SOCS1, SOD2, RBP4, HLA-B, HLA-G, PPP2R1A, TAP1) or down-regulated (IL18, TF, C4BPA, C1QA, C1QB, TYROBP). One mechanism, regulation of complement activation, may have been blocked in HR (PRRSV susceptible) pigs and accounted for the poor clearance of PRRSV by infected macrophages. Multiple inhibiting signals may have prevented effective immune responses in susceptible HR pigs, although some protective genes were up-regulated in these pigs. It is likely that in HR pigs expression of genes associated with protection was delayed, so that the immune response was not stimulated early; thus PRRSV infection had prevented protective immune responses.