THE NOVEL INFLUENZA VIRUS H7N9 PEPTIDE ACTIVATES THE INFLAMMASOME — ASN Events
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  3. THE NOVEL INFLUENZA VIRUS H7N9 PEPTIDE ACTIVATES THE INFLAMMASOME

THE NOVEL INFLUENZA VIRUS H7N9 PEPTIDE ACTIVATES THE INFLAMMASOME (#149)

Anita Pinar 1 , Michelle Tate 1 , Jennifer Dowling 1 , Ashley Mansell 1
  1. Centre of Innate Immunity And Infectious Diseases, Monash Institute Of Medical Research - Prince Henry's Institute Institute Of Medical Research, Melbourne, Vic, Australia

Background: Influenza virus is the major cause of respiratory tract infections resulting in severe immunopathologies. Understanding the molecular basis for disease severity is vital for predicting potential emerging influenzas. The recently emerged H7N9 virus isolated from human disease cases are associated with increased risk of virulence and transmissibility. Understanding the elements of H7N9 induced disease severity during virus infection and pathophysiology is vital for clinical management of high-risk cases and providing valuable insights into the pathogenesis of H7N9 virus infection.

Aim: To examine whether differences between inflammatory and non-inflammatory PB1-F2 strains influences the degree of inflammasome activation and induces influenza pathophysiology.

Methods: Human peripheral blood mononuclear cells (hPBMCs) were primed with LPS (50 pg/mL) for 3 h then stimulated with PB1-F2 peptide strains (50 µg/mL) for 6 h. Immortalised wild-type bone marrow macrophages (iBMMs) were primed with LPS (100 ng/mL) for 3 h prior to stimulation with the H7N9 peptide at a range of doses (10-100 µg/mL) for 6 h. Supernatants were assayed via ELISA for levels of IL-1β protein expression as evidence of inflammasome activation. Cerulean-tagged ASC iBMMs were also stimulated with H7N9 peptide (100 µg/mL) and imaged as time-lapse for 2 h for the visual formation of cerulean ASC specks indicative of inflammasome activation.

Results: Stimulation of hPBMCs with the different PB1-F2 influenza peptides (50 µg/mL) for 6 h induced inflammasome activation as evidenced by the increased levels of IL-1β detected compared to control cells. H7N9 (10-100 µg/mL) stimulation of iBMMs induced inflammasome activation as evidenced by the increased levels of IL-1β detected compared to control cells. H7N9 (100 µg/mL) stimulation of cerulean-tagged ASC iBMMs increased ASC speck formation visually indicative of inflammasome activation compared to control cells.

Conclusion: Pandemic PB1-F2 strains potently activate the inflammasome in hPBMCs. The novel H7N9 influenza peptide potently activates the inflammasome in iBMMs. Understanding the regulation of inflammasome activation during influenza infection is essential for improving influenza disease therapeutics.