Transcriptomic Analysis Reveals Potential of HP-PRRSV to Modulate Immune System Activation Related to Host Pathogen and Damage Associated Signaling in Infected Porcine Monocytes

Background: The production of swine has long been an agricultural and economic staple of the farming and food industry of many countries. One of the largest risks to the continued stability of the swine industry is by pathogens like porcine reproductive and respiratory syndrome virus (PRRSV) that can decimate production as it spreads among individuals. These infections can be low or highly pathogenic, and because it infects monocytic cells, PRRSV can undermine the innate immune response. This is especially true of the interferon stimulated inflammatory response. To shed light on the effect of PRRSV pathogenicity on activation status of the immune response, we polarized infected and control monocyte-derived dendritic cells (mDCs), applied transcriptomic analysis, and predicted protein-protein interactions as networks to elucidate the interconnected biological processes related to low and highly pathogenic PRRSV infection.

Results: Differentially expressed genes (DEGs) from each polarized/unpolarized and PRRSV infected/ uninfected comparison was used to predict networks and subsequent molecular functions affected by the viruses and mediators. The analysis uncovered previously uncharacterized evidence of the ability of PRRSV to effect M1 activation by altering expression of genes related to viral defense, the extra-cellular matrix (ECM), toll-like receptor (TLR) signaling, and damage induced inflammatory signaling.

Conclusion: Genes showing variability in expression, as well as the most common predicted biological network from the comparisons, were related to cellular structure and inflammatory immune responses. These results supply additional insight into the interplay of PRRSV pathogenicity and immune system evasion by affecting multiple routes of host inflammatory signaling, as well as mDC polarization.