Influenza A virus abrogates IFN-gamma response in respiratory epithelial cells by disruption of the Jak/Stat pathway
| Autor: | Serpil C. Erzurum, Tadamichi Meguro, Toshinori Kamisako, Hiroshi Ogawa, Miki Hiroi, Kohsaku Uetani, Yoshihiro Ohmori |
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| Rok vydání: | 2008 |
| Předmět: |
Immunology
Blotting Western Gene Expression Respiratory Mucosa medicine.disease_cause Models Biological Interferon-gamma GTP-Binding Proteins Cell Line Tumor Influenza A virus medicine CIITA Immunology and Allergy Humans Indoleamine-Pyrrole 2 3 -Dioxygenase Phosphorylation Receptors Interferon A549 cell MHC class II Innate immune system Microscopy Confocal biology Reverse Transcriptase Polymerase Chain Reaction NF-kappa B virus diseases JAK-STAT signaling pathway Interferon-alpha Nuclear Proteins Epithelial Cells HLA-DR Antigens Interferon-Stimulated Gene Factor 3 Janus Kinase 1 Intercellular Adhesion Molecule-1 Virology STAT1 Transcription Factor Cell culture biology.protein Trans-Activators Interferon Regulatory Factor-1 Signal Transduction |
| Zdroj: | European journal of immunology. 38(6) |
| ISSN: | 0014-2980 |
| Popis: | The innate immunity to viral infections induces a potent antiviral response mediated by interferons (IFN). Although IFN-gamma is detected during the acute stages of illness in the upper respiratory tract secretions and in the serum of influenza A virus-infected individuals, control of influenza A virus is not dependent upon IFN-gamma as evidenced by studies using anti-IFN-gamma Ab and IFN-gamma(-/-) mice. Thus, we hypothesized that IFN-gamma is not critical in host survival because influenza A virus has mechanisms to evade the antiviral activity of IFN-gamma. To test this, A549 cells, an epithelial cell line derived from lung adenocarcinoma, were infected with influenza virus strain A/Aichi/2/68 (H3N2) (Aichi) and/or stimulated with IFN-gamma to detect IFN-gamma-stimulated MHC class II expression. Influenza A virus infection inhibited IFN-gamma-induced up-regulation of HLA-DRalpha mRNA and the IFN-gamma induction of class II transactivator (CIITA), an obligate mediator of MHC class II expression. Nuclear translocation of Stat1alpha upon IFN-gamma stimulation was significantly inhibited in influenza A virus-infected cells and this was associated with a decrease in Tyr701 and Ser727 phosphorylation of Stat1alpha. Thus, influenza A virus subverts antiviral host defense mediated by IFN-gamma through effects on the intracellular signaling pathways. |
| Databáze: | OpenAIRE |
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