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When the influenza virus enters our respiratory system, it triggers a cascade of rapid reactions involving a large number of proteins. The researchers wanted to discern the role of one such protein, protease-activated receptor 2 (PAR2), which is present in large quantities on the tracheal epithelium.

PAR2 was already known to be an important component of the body's immune response. However, its role in viral infections has only been surmised but never demonstrated in animals until now.

To study the role of PAR2 in the infectious process, the researchers first infected mice with an H1N1 reference strain used as a laboratory model.* They then intranasally administered a PAR2 activator - a small peptide that attaches to the protein’s active site - to activate it. The treatment triggered the release of high levels of a cytokine known as IFNγ. IFNγ is a protein with known anti-viral properties. It blocks viral replication, thus preventing infection from spreading. Thanks to PAR2 activation, mice survived what would have been an otherwise fatal infection.

Moreover, for reasons that have yet to be found, PAR2 activation also dampened the severe pulmonary inflammation that is caused by the body’s excessive response to the pathogen.

The results in mice represent an additional step in understanding the role played by PAR2 in the immune response to the influenza virus. Further studies are needed to validate these results and to translate basic research into a treatment.

“The advantage of this strategy, compared with the usual arsenal against flu (antiviral drugs, vaccines), is that it targets infected cells instead of the virus itself," the researchers explained. “This means that the treatment may be effective against all flu virus strain, and remain so in spite of the strategies used by the virus to resist existing treatments."

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* the H1N1 reference virus used in this study, which began in 2006, is a model virus that has been used worldwide for years by laboratories working on influenza. It is fatal to mice but does not cause disease in humans.

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Reference:

“Protective Role for Protease-Activated Receptor-2 against Influenza Virus Pathogenesis via an IFN-gamma-Dependent Pathway”.

The Journal of Immunology, 15 june 2009,Volume 182 : 7795-7802, No. 12
Khaled Khoufache 1, Fanny LeBouder 1, Eric Morello 1, Fabrice Laurent 2, Sabine Riffault 1, Patricia Andrade-Gordon 3, Severine Boullier 4, 5, Perrine Rousset 6, Nathalie Vergnolle 5, 6, 7 , and Béatrice Riteau 1
1 Molecular Virology and Immunology Unit, Research Unit 892, French National Institute for Agricultural Research (INRA), Domaine de Vilvert, Jouy-en-Josas, France.

2 Infectious Diseases and Veterinary Public Health Research Unit, Research Unit 1282, Infectious Diseases and Veterinary Public Health, INRA, Tours Research centre, Nouzilly France.

3 Johnson and Johnson Pharmaceutical Research and Development, Spring House, PA 19477.

4 INRA, Joint Research Unit 1225, University of Toulouse, National Veterinary College of Toulouse, Toulouse, France;

5 University of Toulouse III Paul Sabatier, Toulouse, France;

6 National Institute of Health and Medical Research (Inserm), Unit 563, Physiopathology centre of Toulouse Purpan, Toulouse, France.

7 Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada.