Regulation of IFN-alpha/beta, MxA, 2',5'-oligoadenylate synthetase, and HLA gene expression in influenza A-infected human lung epithelial cells.
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.
Ronni
T
T
Department of Virology, National Public Health Institute, Helsinki, Finland.
Matikainen
S
S
Sareneva
T
T
Melén
K
K
Pirhonen
J
J
Keskinen
P
P
Julkunen
I
I
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics*; D000230:Adenocarcinoma; D000998:Antiviral Agents / Q000235:genetics*; D004848:Epithelium / Q000378:metabolism / Q000821:virology; D005434:Flow Cytometry; D019204:GTP-Binding Proteins; D015967:Gene Expression Regulation, Viral / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D007251:Influenza, Human / Q000235:genetics* / Q000276:immunology / Q000821:virology; D007370:Interferon Type I / Q000096:biosynthesis / Q000235:genetics*; D016899:Interferon-beta / Q000235:genetics; D007700:Kinetics; D008168:Lung / Q000378:metabolism / Q000821:virology*; D008175:Lung Neoplasms; D064547:Myxovirus Resistance Proteins; D016328:NF-kappa B / Q000378:metabolism; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D011485:Protein Binding / Q000235:genetics; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D014758:Viral Core Proteins / Q000235:genetics; D014764:Viral Proteins / Q000096:biosynthesis
D000998:Antiviral Agents; D006680:HLA Antigens; D007370:Interferon Type I; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D016328:NF-kappa B; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D011506:Proteins; D012333:RNA, Messenger; D014758:Viral Core Proteins; D014764:Viral Proteins; D016899:Interferon-beta; D015088:2',5'-Oligoadenylate Synthetase; D019204:GTP-Binding Proteins