Β-Defensin-1 Regulates Influenza Virus Infection in Human Bronchial Epithelial Cells Through the STAT3 Signaling Pathway

Details

• Personal Author:
  Noti JD ; Othumpangat S
• Description:
  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 respiratory tract epithelial cells and antimicrobial proteins generated by these cells. The antimicrobial peptide, ß-defensin-1, has antiviral activity against both enveloped and non-enveloped viruses. Significant downregulation of ß-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, plaque assay, and confocal microscopy. DEFB1 expression after transfection with two micro RNAs (miRNAs), hsa-miR-186-5p and hsa-miR-340-5p, provided evidence that DEFB1 expression could be modulated by these 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 PCR array analysis of 84 transcription factors, either overexpressing DEFB1 or siRNA silencing of DEFB1 expression significantly modulated the expression of signal transducer and activator of transcription 3 (STAT3). In addition, Ingenuity Pathway Analysis (IPA) integrated with PCR array data showed that the JAK1/STAT3 pathway was significantly altered in cells overexpressing DEFB1, suggesting this to 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 ß-defensin-1 plays a key role in regulating IAV survival through STAT3 and is a potential target for antiviral drug development. [Description provided by NIOSH]
• Subjects:
  Communicable Diseases Immune System Influenza, Human Occupational Health Respiratory System Respiratory Tract Diseases Safety Viral Diseases
• Keywords:
  Author Keywords: DEFB1 Bronchial Epithelial Cells Cell Signaling Gene Expression Immune Reaction Influenza Influenza Virus MiRNA Pathogens Proteins Respiratory Infections STAT Pathway Viral Diseases

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• ISSN:
  2076-0817
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  12
• Issue:
  1
• NIOSHTIC Number:
  nn:20066839
• Citation:
  Pathogens 2023 Jan; 12(1):123
• Contact Point Address:
  Sreekumar Othumpangat, Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV 26505, USA
• Email:
  seo8@cdc.gov
• Federal Fiscal Year:
  2023
• NORA Priority Area:
  Healthcare and Social Assistance
• Peer Reviewed:
  True
• Source Full Name:
  Pathogens
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:35f39011f23e128f6bc09d35fed76c6200bb15a1c0f3abbf772c812478382b83412bded0c28e429853baa213d613f73a1fcb01479acf5673c4fc2b3165da1df7
• Download URL:
  https://stacks.cdc.gov/view/cdc/231172/cdc_231172_DS1.pdf
• File Type:
  [PDF - 6.66 MB ]