Influenza Virus Infection Modulates the Death Receptor Pathway During Early Stages of Infection in Human Bronchial Epithelial Cells

Details

• Personal Author:
  Beezhold, Donald H. ; Noti JD ; Othumpangat S
• Description:
  Host-viral interaction occurring throughout the infection process between the influenza A virus (IAV) and bronchial cells determines the success of infection. Our previous studies showed that the apoptotic pathway triggered by the host cells was repressed by IAV facilitating prolonged survival of infected cells. A detailed understanding on the role of IAV in altering the cell death pathway during early stage infection of human bronchial epithelial cells (HBEpCs) is still unclear. We investigated the gene expression profiles of IAV-infected versus mock-infected cells at the early stage of infection using a PCR array for death receptor (DR) pathway. At early stages infection (2h) with IAV significantly upregulated DR pathway genes in HBEpCs, whereas 6h exposure to IAV resulted in downregulation of same genes. IAV replication in HBEpCs decreased the levels of DR pathway genes including TNF-receptor super family1, Fas-associated Death Domain, caspase-8, and caspase-3, by 6h, resulting in increased survival of cells. The apoptotic cell population decreased in 6h compared to the 2h exposure to IAV. The PCR array data was imported into Ingenuity pathway analysis software, resulting in confirmation of the model showing significant modulation of the DR pathway. Our data indicate that a significant transcriptional regulation of apoptotic, necrotic and DR genes occur at early and late hours of infection that are vital in modulating the survival of host cells and replication of IAV. These data intuitively may have provided a likely roadmap for translational approaches targeting the DR pathway to enhance apoptosis and inhibit replication of the virus. [Description provided by NIOSH]
• Subjects:
  Communicable Diseases Immune System Influenza, Human Lung Microbiology Occupational Health Respiratory System Safety Viral Diseases
• Keywords:
  Apoptosis Author Keywords: Death Recepotor Caspase-8 Cell Alteration Cell Death Cell Signaling Cellular Effects Cellular Reactions Exposure Assessment Gene Expression Gene Regulation Genomics Immune System Infection Control Infectious Agents Infectious Diseases Influenza Influenza Virus Lung Cells Lung Epithelial Cells Microscopic Analysis Proteins Signaling Pathways Viral Diseases Viral Infections

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• ISSN:
  1094-8341
• 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:
  50
• Issue:
  9
• NIOSHTIC Number:
  nn:20052006
• Citation:
  Physiol Genomics 2018 Sep; 50(9):770-779
• 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:
  2018
• NORA Priority Area:
  Healthcare and Social Assistance
• Peer Reviewed:
  True
• Source Full Name:
  Physiological Genomics
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:3d854003f41f2b5a51bccf277439782840e8dd948b40e78eb1373eed5ca0a8564c32ddf5ea126546f8a4cdba6173d85bf6a887f9ffa1936d624f6af64af253a4
• Download URL:
  https://stacks.cdc.gov/view/cdc/211637/cdc_211637_DS1.pdf
• File Type:
  [PDF - 538.22 KB ]