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-β to the COX-1 promoter by luciferase reporter and chromatin immunoprecipitation assays. In addition, silencing of C/EBP-β 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-β 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. IMPORTANCE The 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.