title: The Influenza Virus Protein PB1-F2 Increases Viral Pathogenesis through Neutrophil Recruitment and NK Cells Inhibition.
abstract: 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.
authors: VIM, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors: Aurore
authors: A
authors: Vidy
authors: VIM, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors: Pauline
authors: P
authors: Maisonnasse
authors: VIM, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors: Bruno
authors: B
authors: Da Costa
authors: VIM, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors: Bernard
authors: B
authors: Delmas
authors: VIM, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors: Christophe
authors: C
authors: Chevalier
authors: VIM, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors: Ronan
authors: http://orcid.org/0000-0002-2012-0064
authors: R
authors: Le Goffic
mesh_terms: D000818:Animals; D005260:Female; D007249:Inflammation / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology*; D008156:Luciferases / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D009503:Neutropenia / Q000150:complications / Q000473:pathology; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000473:pathology; D009976:Orthomyxoviridae Infections / Q000150:complications / Q000276:immunology* / Q000401:mortality / Q000821:virology*; D013601:T-Lymphocytes / Q000473:pathology; D059467:Transcriptome / Q000235:genetics; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; C442816:PB1-F2 protein, Influenza A virus; D014764:Viral Proteins; D008156:Luciferases