The Influenza Virus Protein PB1-F2 Increases Viral Pathogenesis through Neutrophil Recruitment and NK Cells Inhibition

Aurore Vidy-Roche (1, 2) , Pauline Maisonnasse (1, 2) , Bruno da Costa (1, 2) , Bernard Delmas (1, 2) , Christophe Chevalier (1, 2) , Ronan Le Goffic (1, 2)

1 VIM (UR 0892) - Unité de recherche Virologie et Immunologie Moléculaires
2 Université Paris-Saclay

The influenza A virus (IAV) PB1-F2 protein is a virulence factor contributing to the pathogenesis observed during IAV infections in mammals. In this study, using a mouse model, we compared the host response associated with PB1-F2 with an early transcriptomic signature that was previously associated with neutrophils and consecutively fatal IAV infections. This allowed us to show that PB1-F2 is partly involved in neutrophil-related mechanisms leading to death. Using neutropenic mice, we confirmed that the harmful effect of PB1-F2 is due to an excessive inflammation mediated by an increased neutrophil mobilization. We identified the downstream effects of this PB1-F2-exacerbated neutrophil recruitment. PB1-F2 had no impact on the lymphocyte recruitment in the airways at day 8 pi. However, functional genomics analysis and flow cytometry in broncho-alveolar lavages at 4 days pi revealed that PB1-F2 induced a NK cells deficiency. Thus, our results identify PB1-F2 as an important immune disruptive factor during the IAV infection.

Mots clés: epithelial-cells; lung injury; hemagglutinins; expression; pneumonia; activation; recognition; inflammation; mice; infected cells

Domaines: Sciences du Vivant [q-bio]

Aurore Vidy-Roche, Pauline Maisonnasse, Bruno da Costa, Bernard Delmas, Christophe Chevalier, et al.. The Influenza Virus Protein PB1-F2 Increases Viral Pathogenesis through Neutrophil Recruitment and NK Cells Inhibition. PLoS ONE, 2016, 11 (10), pp.1-19. ⟨10.1371/journal.pone.0165361⟩. ⟨hal-01608535⟩