Inhibitory activity and molecular mechanism of protegrin-1 against porcine reproductive and respiratory syndrome virus in vitro

Background: Porcine reproductive and respiratory syndrome virus (PRRSV) causes severe diseases affecting the swine industry worldwide. Currently, no vaccination regimen has proven sustained success in preventing PRRSV infection. Therefore, there is an urgent need for new antiviral strategies to control PRRSV. In this study, the inhibitory effects and molecular mechanism of antimicrobial peptide protegrin-1 (PG-1) isolated from porcine leukocytes against PRRSV were evaluated in vitro. Methods: Marc-145 cells or porcine alveolar macrophages (PAMs) were infected with PRRSV in the presence or absence of PG-1 for 36 h. The inhibitory effects of PG-1 were assessed by measuring the transcript and protein level of PRRSV ORF7 in cells and virus titres in the supernatants. Virus attachment and entry assays were performed to explore the molecular mechanism of PG-1 action. Results: We demonstrated that PG-1 strongly inhibited PRRSV infection and replication by suppressing virus RNA and protein synthesis, virus progeny production and viral particles release. Furthermore, in the PRRSV life cycle, PG-1 mainly blocked viral attachment in Marc-145 cells. However, in PAMs, PG-1 could neither inhibit PRRSV replication nor elevate antiviral cytokine expression. Conclusions: Our findings for the first time show that PG-1 is an antiviral peptide with effective inhibitory effects on PRRSV infection and replication in Marc-145 cells.