Scientific article

H5N1 virus activates signaling pathways in human endothelial cells resulting in a specific imbalanced inflammatory response

Published inThe Journal of immunology, vol. 186, no. 1, p. 164-173
Publication date2011

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.

  • Cell Communication/genetics/immunology
  • Cells, Cultured
  • Endothelium, Vascular/immunology/metabolism/virology
  • Gene Expression Profiling
  • HMGA1a Protein/metabolism/physiology
  • Humans
  • Inflammation/immunology/prevention & control/virology
  • Inflammation Mediators/metabolism/physiology
  • Influenza A Virus, H1N1 Subtype/immunology
  • Influenza A Virus, H5N1 Subtype/growth & development/immunology
  • Influenza, Human/immunology/virology
  • Interferon Regulatory Factor-3/physiology
  • Interferon Regulatory Factor-7/physiology
  • Oligonucleotide Array Sequence Analysis
  • Signal Transduction/genetics/immunology
Affiliation Not a UNIGE publication
Citation (ISO format)
VIEMANN, Dorothee et al. H5N1 virus activates signaling pathways in human endothelial cells resulting in a specific imbalanced inflammatory response. In: The Journal of immunology, 2011, vol. 186, n° 1, p. 164–173. doi: 10.4049/jimmunol.0904170
Main files (1)
Article (Published version)
ISSN of the journal0022-1767

Technical informations

Creation09/22/2015 3:59:00 PM
First validation09/22/2015 3:59:00 PM
Update time03/14/2023 11:38:01 PM
Status update03/14/2023 11:38:00 PM
Last indexation08/29/2023 7:12:45 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack