Elucidating Porcine Reproductive and Respiratory Virus (PRRSV) Induced Changes in the Molecular Regulatory Networks of Alveolar Macrophages

Porcine Reproductive and Respiratory Syndrome (PRRS) is a contagious viral disease in pigs characterized by poor reproductive health, increased mortality, and reductions in growth rates. PRRS is caused by PRRS Virus (PRRSV). To better understand PRRSV pathogenesis and the host’s response to PRRSV infection, we performed regulatory and transcriptome studies in PRRSV-infected porcine alveolar macrophages (PAMs), which is the natural host.  PRRSV-induced changes in the PAM transcriptome were characterized from PAMs infected with PRRSV (VR-2332) at an M.O.I. of ten or from mock-infected controls. RNA was collected at 12, 24, or 48 hpi and sequenced. Differential expression analysis revealed that 676 genes were significantly (p<0.05) altered in at least one time point. The top Gene Ontology classes included genes that participate in defense response, inflammatory response, cytokine-cytokine receptor interaction, and regulation of programmed cell death.  For regulatory analyses, we employed a yeast-one hybrid scheme to understand the regulation of microRNA (miRNA), which we have previously found to be altered in PRRSV-infected PAMs. Our analysis indicated that miR-147, which is down-regulated in PRRSV-infected PAMs, may be regulated by TCF7L1, BACH1, GTF2A2, and GTF3A, which are known to regulate Wnt signaling and IL4 signaling events during T-cell responses to infections.  Furthermore, miR-380, which is up-regulated in PRRSV-infected PAMs, may be regulated by BATF, BCLAF1, and WWTR1, which are known to regulate immune cell differentiation and activation and apoptosis.  Taken together, the observed changes in regulatory and transcriptome elements suggest that PRRSV infection induces complex changes in the host molecular regulatory networks.