Regulation of IFN-alpha/beta, MxA, 2',5'-oligoadenylate synthetase, and HLA gene expression in influenza A-infected human lung epithelial cells

J Immunol. 1997 Mar 1;158(5):2363-74.


The epithelial cells of the respiratory tract are the primary sites of virus replication in influenza A virus infections. We infected human alveolar epithelium-like A549 cells and fibroblast-like human fetal lung (HFL1) cells with a pathogenic influenza A virus (A/Beijing/353/89), and studied the kinetics of infection and the expression of host IFN-alpha/beta, MxA, OAS (2',5'-oligoadenylate synthetase), and HLA class I and II genes. Viral mRNA and protein synthesis was clearly seen in virus-infected lung cells. A549 and HFL1 cells produced only small amounts of IFN-alpha/beta, whereas virus-infected macrophages produced type I IFN very efficiently. The kinetics of IFN-beta gene expression in A549 cells was rapid, as shown by reverse-transcriptase PCR, and IFN-beta mRNA expression levels correlated well to the kinetics of nuclear factor-kappa B transcription factor activation. In influenza A virus-infected A549 and HFL1 cells, MxA gene induction was mediated by IFN-alpha/beta released into the cell culture supernatant, and was prevented by anti-type I IFN Abs. HLA class I Ag expression, which could be activated by IFN in noninfected A549 and HFL1 cells, was not induced in these cells by virus infection. The results suggest that type I IFN are essential for the activation of the antiviral response in lung epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / genetics*
  • Adenocarcinoma
  • Antiviral Agents / genetics*
  • Epithelium / metabolism
  • Epithelium / virology
  • Flow Cytometry
  • GTP-Binding Proteins*
  • Gene Expression Regulation, Viral / immunology*
  • HLA Antigens / genetics*
  • Humans
  • Influenza A virus / immunology
  • Influenza, Human / genetics*
  • Influenza, Human / immunology
  • Influenza, Human / virology
  • Interferon Type I / biosynthesis
  • Interferon Type I / genetics*
  • Interferon-beta / genetics
  • Kinetics
  • Lung / metabolism
  • Lung / virology*
  • Lung Neoplasms
  • Myxovirus Resistance Proteins
  • NF-kappa B / metabolism
  • Nucleocapsid Proteins
  • Nucleoproteins*
  • Protein Binding / genetics
  • Protein Biosynthesis
  • Proteins / genetics*
  • RNA, Messenger / biosynthesis
  • Transcriptional Activation
  • Tumor Cells, Cultured
  • Viral Core Proteins / genetics
  • Viral Proteins / biosynthesis


  • Antiviral Agents
  • HLA Antigens
  • Interferon Type I
  • MX1 protein, human
  • Myxovirus Resistance Proteins
  • NF-kappa B
  • Nucleocapsid Proteins
  • Nucleoproteins
  • Proteins
  • RNA, Messenger
  • Viral Core Proteins
  • Viral Proteins
  • Interferon-beta
  • 2',5'-Oligoadenylate Synthetase
  • GTP-Binding Proteins