Influenza A Virus Protein PB1-F2 Exacerbates IFN-b Expression of Human Respiratory Epithelial Cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Immunology Année : 2010

Influenza A Virus Protein PB1-F2 Exacerbates IFN-b Expression of Human Respiratory Epithelial Cells

Résumé

The PB1-F2 protein of the influenza A virus (IAV) contributes to viral pathogenesis by a mechanism that is not well understood. PB1-F2 was shown to modulate apoptosis and to be targeted by the CD8+ T cell response. In this study, we examined the downstream effects of PB1-F2 protein during IAV infection by measuring expression of the cellular genes in response to infection with wild-type WSN/33 and PB1-F2 knockout viruses in human lung epithelial cells. Wild-type virus infection resulted in a significant induction of genes involved in innate immunity. Knocking out the PB1-F2 gene strongly decreased the magnitude of expression of cellular genes implicated in antiviral response and MHC class I Ag presentation, suggesting that PB1-F2 exacerbates innate immune response. Biological network analysis revealed the IFN pathway as a link between PB1-F2 and deregulated genes. Using quantitative RT-PCR and IFN-β gene reporter assay, we determined that PB1-F2 mediates an upregulation of IFN-β expression that is dependent on NF-κB but not on AP-1 and IFN regulatory factor-3 transcription factors. Recombinant viruses knocked out for the PB1-F2 and/or the nonstructural viral protein 1 (the viral antagonist of the IFN response) genes provide further evidence that PB1-F2 increases IFN-β expression and that nonstructural viral protein 1 strongly antagonizes the effect of PB1-F2 on the innate response. Finally, we compared the effect of PB1-F2 variants taken from several IAV strains on IFN-β expression and found that PB1-F2–mediated IFN-β induction is significantly influenced by its amino acid sequence, demonstrating its importance in the host cell response triggered by IAV infection.

Domaines

Immunologie

Dates et versions

hal-01193647 , version 1 (04-09-2015)

Identifiants

Citer

Ronan Le Goffic, Edwige Bouguyon, Christophe Chevalier, Jasmina Vidic, Bruno da Costa, et al.. Influenza A Virus Protein PB1-F2 Exacerbates IFN-b Expression of Human Respiratory Epithelial Cells. Journal of Immunology, 2010, 185 (8), pp.4812-4823. ⟨10.4049/jimmunol.0903952⟩. ⟨hal-01193647⟩
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