PMID:23202729

Citation	Khoufache, K, Berri, F, Nacken, W, Vogel, AB, Delenne, M, Camerer, E, Coughlin, SR, Carmeliet, P, Lina, B, Rimmelzwaan, GF, Planz, O, Ludwig, S and Riteau, B (2013) PAR1 contributes to influenza A virus pathogenicity in mice. J. Clin. Invest. 123:206-14
Abstract	Influenza causes substantial morbidity and mortality, and highly pathogenic and drug-resistant strains are likely to emerge in the future. Protease-activated receptor 1 (PAR1) is a thrombin-activated receptor that contributes to inflammatory responses at mucosal surfaces. The role of PAR1 in pathogenesis of virus infections is unknown. Here, we demonstrate that PAR1 contributed to the deleterious inflammatory response after influenza virus infection in mice. Activating PAR1 by administering the agonist TFLLR-NH2 decreased survival and increased lung inflammation after influenza infection. Importantly, both administration of a PAR1 antagonist and PAR1 deficiency protected mice from infection with influenza A viruses (IAVs). Treatment with the PAR1 agonist did not alter survival of mice deficient in plasminogen (PLG), which suggests that PLG permits and/or interacts with a PAR1 function in this model. PAR1 antagonists are in human trials for other indications. Our findings suggest that PAR1 antagonism might be explored as a treatment for influenza, including that caused by highly pathogenic H5N1 and oseltamivir-resistant H1N1 viruses.
Links	PubMed PMC3533265 Online version:10.1172/JCI61667
Keywords	Animals; Dogs; Humans; Influenza A Virus, H1N1 Subtype/pathogenicity; Influenza A Virus, H5N1 Subtype/pathogenicity; Influenza, Human/drug therapy; Influenza, Human/genetics; Influenza, Human/immunology; Mice; Mice, Knockout; NIH 3T3 Cells; Oligopeptides/pharmacology; Orthomyxoviridae Infections/drug therapy; Orthomyxoviridae Infections/genetics; Orthomyxoviridae Infections/immunology; Orthomyxoviridae Infections/pathology; Plasminogen/genetics; Plasminogen/immunology; Receptor, PAR-1/agonists; Receptor, PAR-1/antagonists & inhibitors; Receptor, PAR-1/genetics; Receptor, PAR-1/immunology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
AZOL4:G7ZFL4		GO:0002534: cytokine production involved in inflammatory response	ECO:0000314:		P		see figure 2 for the results of the direct assay and the proof that the protein produces cytokine that is involved in inflammatory responce	complete CACAO 7391

References

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