β-defensin-1 regulates influenza virus infection in human bronchial epithelial cells through the STAT3 signaling pathway

Understanding the host response to influenza A virus (IAV) infection is vital for developing intervention strategies. The primary barriers for invading respiratory pathogens are the airway epithelial cells of the respiratory tract and antimicrobial peptides produced by these cells. The antimicrobial peptide, β-defensin-1, has antiviral activity against both enveloped and non-enveloped viruses. Significant downregulation of β-defensin1 gene (DEFB1) expression was observed when human bronchial epithelial cells (HBEpCs) were exposed to IAV. HBEpCs overexpressing DEFB1 caused a significant reduction in IAV, that was confirmed by IAV matrix gene analysis and confocal microscopy. DEFB1expression after transfection with hsa-miR-186-5p and hsa-miR-340-5p provided evidence that DEFB1 expression could be modulated by these two miRNAs and hsa-miR-186-5p had a higher binding efficiency with DEFB1. Overexpression of DEFB1 in IAV infected HBEpCs led to increased NF-kB expression. In a Polymerase Chain Reaction (PCR) array analysis of 84 transcription factors, either overexpressing DEFB1 or siRNA silencing of DEFB1 expression significantly modulated the expression of STAT3. In addition, Ingenuity Pathway Analysis (IPA) integrated with PCR array data showed that the JAK1/STAT3 pathway was significantly altered by cells overexpressing DEFB1, suggesting that this may be one of the pathways by which defensin regulates IAV replication in HBEpCs. In conclusion, the reduction in IAV copy number in DEFB1 overexpressing cells suggests that β-defensin-1 plays a key role in regulating IAV survival through STAT3 and is a potential target for antiviral drug development.