Plasminogen controls inflammation and pathogenesis of influenza virus infections via fibrinolysis.

Abstract

Detrimental inflammation of the lungs is a hallmark of severe influenza virus infections. Endothelial cells are the source of cytokine amplification, although mechanisms underlying this process are unknown. Here, using combined pharmacological and gene-deletion approaches, we show that plasminogen controls lung inflammation and pathogenesis of infections with influenza A/PR/8/34, highly pathogenic H5N1 and 2009 pandemic H1N1 viruses. Reduction of virus replication was not responsible for the observed effect. However, pharmacological depletion of fibrinogen, the main target of plasminogen reversed disease resistance of plasminogen-deficient mice or mice treated with an inhibitor of plasminogen-mediated fibrinolysis. Therefore, plasminogen contributes to the deleterious inflammation of the lungs and local fibrin clot formation may be implicated in host defense against influenza virus infections. Our studies suggest that the hemostatic system might be explored for novel treatments against influenza.

• Authors: Fatma Berri, Guus F Rimmelzwaan, Michel Hanss, Emmanuel Albina, Marie-Laure Foucault-Grunenwald, Vuong B Lê, Stella E Vogelzang-van Trierum, Patrica Gil, Eric Camerer, Dominique Martinez, Bruno Lina, Roger Lijnen, Peter Carmeliet, Béatrice Riteau
• Journal: PLoS pathogens (PLoS Pathog) Vol. 9 Issue 3 Pg. e1003229 (Mar 2013) ISSN: 1553-7374 [Electronic] United States
• PMID: 23555246 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Fibrinolytic Agents
• Fibrin
• Fibrinogen
• Plasminogen

Topics

• Animals
• Antiviral Agents (pharmacology)
• Female
• Fibrin (drug effects)
• Fibrin Clot Lysis Time
• Fibrinogen (drug effects)
• Fibrinolysis (drug effects)
• Fibrinolytic Agents (pharmacology)
• Host-Pathogen Interactions
• Inflammation (chemically induced, prevention & control)
• Influenza A Virus, H1N1 Subtype (pathogenicity)
• Influenza A Virus, H5N1 Subtype (pathogenicity)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Orthomyxoviridae Infections (drug therapy, prevention & control)
• Plasminogen (deficiency, genetics, pharmacology)
• Pneumonia, Viral (drug therapy, prevention & control)
• Virus Replication (drug effects)