Influenza virus infection modulates the death receptor pathway during early stages of infection in human bronchial epithelial cells

Details

• Alternative Title:
  Physiol Genomics
• Personal Author:
  Othumpangat, Sreekumar ; Beezhold, Donald H. ; Noti, John D.
• 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 vs. mock-infected cells at the early stage of infection with a PCR array for death receptor (DR) pathway. At early stages infection (2 h) with IAV significantly upregulated DR pathway genes in HBEpCs, whereas 6 h exposure to IAV resulted in downregulation of the same genes. IAV replication in HBEpCs decreased the levels of DR pathway genes including TNF-receptor superfamily 1, Fas-associated death domain, caspase-8, and caspase-3 by 6 h, resulting in increased survival of cells. The apoptotic cell population decreased in 6 h compared with the 2 h exposure to IAV. The PCR array data were 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 may have provided a likely roadmap for translational approaches targeting the DR pathway to enhance apoptosis and inhibit replication of the virus.
• Subjects:
  Apoptosis Article Bronchi Caspase-8 Cell Line Death Receptor Epithelial Cells FADD Gene Expression Regulation Humans Influenza A Virus Influenza Virus Lung Epithelial Cells Necrosis Receptors, Death Domain Signal Transduction

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• Source:
  Physiol Genomics. 50(9):770-779
• Pubmed ID:
  29958081
• Pubmed Central ID:
  PMC6388629
• Document Type:
  Journal Article
• Funding:
  CC999999/Intramural CDC HHS/United States
• Volume:
  50
• Issue:
  9
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:be107d4268a5cf058bd1b7b1c677dd7cc689712ba241a703c0b51f02e1ac2f61
• Download URL:
  https://stacks.cdc.gov/view/cdc/76178/cdc_76178_DS1.pdf
• File Type:
  [PDF - 1.84 MB ]