Upregulation of miRNA-4776 in Influenza Virus Infected Bronchial Epithelial Cells Is Associated with Downregulation of NFKBIB and Increased Viral Survival

Details

• Personal Author:
  Beezhold, Donald H. ; Bryan NB ; Noti JD ; Othumpangat S
• Description:
  Influenza A virus (IAV) infection remains a significant cause of morbidity and mortality worldwide. One key transcription factor that is activated upon IAV infection is nuclear factor Kappa B (NF-kappaB). NF-kappaB regulation involves the inhibitor proteins NF-kappaB inhibitor beta (NFKBIB), (also known as IkappaBbeta), which form complexes with NF-kappaB to sequester it in the cytoplasm. In this study, microarray data showed differential expression of several microRNAs (miRNAs) on exposure to IAV. Target scan analysis revealed that miR-4776, miR-4514 and miR-4742 potentially target NFKBIB messenger RNA (mRNA). Time-course analysis of primary bronchial epithelial cells (HBEpCs) showed that miR-4776 expression is increased within 1 h of infection, followed by its downregulation 4 h post-exposure to IAV. NFKBIB upregulation of miR-4776 correlated with a decrease in NFKBIB expression within 1 h of infection and a subsequent increase in NFKBIB expression 4 h post-infection. In addition, miRNA ago-immunoprecipitation studies and the three prime untranslated region (3' UTR) luciferase assay confirmed that miR-4776 targets NFKBIB mRNA. Furthermore, uninfected HBEpCs transfected with miR-4776 mimic showed decreased expression of NFKBIB mRNA. Overexpression of NFKBIB protein in IAV infected cells led to lower levels of IAV. Taken together, our data suggest that miRNA-4776 modulates IAV production in infected cells through NFKBIB expression, possibly through the modulation of NF-kappaB. [Description provided by NIOSH]
• Subjects:
  Communicable Diseases Immune System Influenza, Human Lung Microbiology Occupational Health Respiratory System Safety Viral Diseases
• Keywords:
  Author Keywords: NFKBIB Bronchial Epithelial Cells Cellular Effects Cellular Reactions Exposure Assessment Gene Expression Gene Regulation Immune System Infectious Agents Infectious Diseases Influenza Influenza Virus Lung Cells Microscopic Analysis NF-kappaB Proteins Ribonucleic Acids RNA Viral Diseases Viral Infections Virus Survival

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• ISSN:
  1999-4915
• 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
• Pages in Document:
  94
• Volume:
  9
• Issue:
  5
• NIOSHTIC Number:
  nn:20049785
• Citation:
  Viruses 2017 May; 9(5):94
• 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:
  2017
• NORA Priority Area:
  Healthcare and Social Assistance
• Peer Reviewed:
  True
• Source Full Name:
  Viruses
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:70f09e0b785537b422fa6464c3e00031fd49811a8bdbbe0a6b01fd05c177a7c8191805607960ac28885f668a98729b4672ed1a04d90d43e5299da57563b41c0a
• Download URL:
  https://stacks.cdc.gov/view/cdc/210415/cdc_210415_DS1.pdf
• File Type:
  [PDF - 965.64 KB ]