H5N1 Virus Activates Signaling Pathways in Human Endothelial Cells Resulting in a Specific Imbalanced Inflammatory Response
| Autor: | Aloys Lueken, Johannes Roth, Mirco Schmolke, Stephan Ludwig, Dorothee Viemann, Helmut Wittkowski, Yvonne Boergeling, Judith Friesenhagen |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Interferon Regulatory Factor-7
Immunology Inflammation/immunology/prevention & control/virology Cell Communication Interferon Regulatory Factor-7/physiology Signal Transduction/genetics/immunology Biology medicine.disease_cause Virus Proinflammatory cytokine Influenza A Virus H1N1 Subtype Influenza Human medicine Influenza A virus Humans Immunology and Allergy HMGA1a Protein Influenza A Virus H5N1 Subtype/growth & development/immunology Transcription factor Cells Cultured HMGA1a Protein/metabolism/physiology Oligonucleotide Array Sequence Analysis Inflammation Cell Communication/genetics/immunology Influenza A Virus H5N1 Subtype Gene Expression Profiling virus diseases HMGA1 Influenza A virus subtype H5N1 Interferon Regulatory Factor-3/physiology Gene expression profiling Influenza A Virus H1N1 Subtype/immunology Endothelium Vascular/immunology/metabolism/virology biology.protein Interferon Regulatory Factor-3 Influenza Human/immunology/virology Endothelium Vascular Inflammation Mediators Signal transduction Inflammation Mediators/metabolism/physiology Signal Transduction |
| Zdroj: | Journal of Immunology, Vol. 186, No 1 (2011) pp. 164-173 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.0904170 |
| Popis: | H5N1 influenza virus infections in humans cause a characteristic systemic inflammatory response syndrome; however, the molecular mechanisms are largely unknown. Endothelial cells (ECs) play a pivotal role in hyperdynamic septic diseases. To unravel specific signaling networks activated by H5N1 we used a genome-wide comparative systems biology approach analyzing gene expression in human ECs infected with three different human and avian influenza strains of high and low pathogenicity. Blocking of specific signaling pathways revealed that H5N1 induces an exceptionally NF-κB–dependent gene response in human endothelia. Additionally, the IFN-driven antiviral program in ECs is shown to be dependent on IFN regulatory factor 3 but significantly impaired upon H5N1 infection compared with low pathogenic influenza virus. As additional modulators of this H5N1-specific imbalanced gene response pattern, we identified HMGA1 as a novel transcription factor specifically responsible for the overwhelming proinflammatory but not antiviral response, whereas NFATC4 was found to regulate transcription of specifically H5N1-induced genes. We describe for the first time, to our knowledge, defined signaling patterns specifically activated by H5N1, which, in contrast to low pathogenic influenza viruses, are responsible for an imbalance of an overwhelming proinflammatory and impaired antiviral gene program. |
| Databáze: | OpenAIRE |
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