Title: PAR1 contributes to influenza A virus pathogenicity in mice
Authors: Khoufache, Khaled ×
Berri, Fatma
Nacken, Wolfgang
Vogel, Annette B
Delenne, Marie
Camerer, Eric
Coughlin, Shaun R
Carmeliet, Peter
Lina, Bruno
Rimmelzwaan, Guus F
Planz, Oliver
Ludwig, Stephan
Riteau, Béatrice #
Issue Date: Jan-2013
Publisher: American Society for Clinical Investigation
Series Title: Journal of Clinical Investigation vol:123 issue:1 pages:206-214
Article number: 61667
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.
ISSN: 0021-9738
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science