title: 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.affiliation: VirPath, EA4610 Virologie et Pathologie Humaine, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Fatma
authors.initials: F
authors.lastname: Berri
authors.forename: Guus F
authors.initials: GF
authors.lastname: Rimmelzwaan
authors.forename: Michel
authors.initials: M
authors.lastname: Hanss
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Albina
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Foucault-Grunenwald
authors.forename: Vuong B
authors.initials: VB
authors.lastname: Lê
authors.forename: Stella E
authors.initials: SE
authors.lastname: Vogelzang-van Trierum
authors.forename: Patrica
authors.initials: P
authors.lastname: Gil
authors.forename: Eric
authors.initials: E
authors.lastname: Camerer
authors.forename: Dominique
authors.initials: D
authors.lastname: Martinez
authors.forename: Bruno
authors.initials: B
authors.lastname: Lina
authors.forename: Roger
authors.initials: R
authors.lastname: Lijnen
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Béatrice
authors.initials: B
authors.lastname: Riteau
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D005260:Female; D005337:Fibrin / Q000187:drug effects; D063285:Fibrin Clot Lysis Time; D005340:Fibrinogen / Q000187:drug effects; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D054884:Host-Pathogen Interactions; D007249:Inflammation / Q000139:chemically induced* / Q000517:prevention & control; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity; D053124:Influenza A Virus, H5N1 Subtype / Q000472:pathogenicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000517:prevention & control; D010958:Plasminogen / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology*; D011024:Pneumonia, Viral / Q000188:drug therapy* / Q000517:prevention & control; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D005343:Fibrinolytic Agents; D005337:Fibrin; D005340:Fibrinogen; D010958:Plasminogen
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