Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Induces Prostaglandin E ₂ Production through Cyclooxygenase 1, Which Is Dependent on the ERK1/2-p-C/EBP-β Pathway

Abstract

Atypical porcine reproductive and respiratory syndrome (PRRS) caused by highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) is characterized by high fever and high mortality. However, the mechanism underlying the fever induction is still unknown. Prostaglandin E 2 (PGE 2 ), synthesized by cyclooxygenase type 1/2 (COX-1/2) enzymes, is essential for inducing fever. In this study, we found that PGE 2 , together with COX-1, was significantly elevated by HP-PRRSV. We subsequently demonstrated that extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated ERK (p-ERK) were the key nodes to trigger COX-1 expression after HP-PRRSV infection. Furthermore, we proved the direct binding of p-C/EBP-␤ to the COX-1 promoter by luciferase reporter and chromatin immunoprecipitation assays. In addition, silencing of C/EBP-␤ remarkably impaired the enhancement of COX-1 production induced by HP-PRRSV infection. Taken together, our results indicate that HP-PPRSV elicits the expression of COX-1 through the ERK1/2-p-C/EBP-␤ signaling pathway, resulting in the increase of PGE 2 , which might be the cause of high fever in infected pigs. Our findings might provide new insights into the molecular mechanisms underlying the pathogenesis of HP-PRRSV infection. IMPORTANCEThe atypical PRRS caused by HP-PRRSV was characterized by high fever, high morbidity, and high mortality in pigs of all ages, yet how HP-PRRSV induces high fever in pigs remains unknown. In the present study, we found out that HP-PRRSV infection could increase PGE 2 production by upregulation of COX-1, and we subsequently characterized the underlying mechanisms about how HP-PRRSV enhances COX-1 production. PGE 2 plays a critical role in inducing high temperature in hosts during pathogen infections. Thus, our findings here could help us have a better understanding of HP-PRRSV pathogenesis.

Isobavachalcone inhibits post-entry stages of the porcine reproductive and respiratory syndrome virus life cycle

“…The ERK signaling pathway has been demonstrated to play an important role in the post-entry steps of the PRRSV replication cycle and to enhance PRRSV infection [15]. The ERK pathway may also contribute to HP-PRRSV pathogenesis [2]. Apoptosis also influences PRRSV replication, since the induction of apoptosis in Marc145 cells increases virus replication [8].…”

Attenuation of highly pathogenic porcine reproductive and respiratory syndrome virus by inserting an additional transcription unit

“…Aliquots of the cell culture supernatant were harvested at the indicated time points post-infection. Viral titration was performed by a standard TCID 50 assay as described previously [21]. Cell death rates were determined by trypan blue exclusion dye staining at 36 h.p.i..…”

Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Induces Interleukin-17 Production via Activation of the IRAK1-PI3K-p38MAPK-C/EBPβ/CREB Pathways

“…In our study, we demonstrate that the increase of IL-17 induced by PRRSV and nsp11 is associated with PI3K and p38MAPK pathways, since PI3K and p38MAPK inhibitors reduce the upregulated IL-17 production. Importantly, PRRSV infection indeed induces the activation of PI3K, p38MAPK, and C/EBP␤ (47)(48)(49). The relationship of PRRSV infection and CREB activation has not been reported before, but many other viruses, including HTLV-1 and varicella-zoster virus, can induce CREB activation (50,51).…”