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Influenza A virus protein PB1-F2 exacerbates IFN-beta expression of human respiratory epithelial cells.
J Immunol 2010; 185(8):4812-23JI

Abstract

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.

Authors+Show Affiliations

Unité de Virologie et Immunologie Moléculaires, Unité de Recherche 892 Institut National de la Recherche Agronomique, Domaine de Vilvert, Jouy-en-Josas, France. ronan.legoffic@jouy.inra.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20844191

Citation

Le Goffic, Ronan, et al. "Influenza a Virus Protein PB1-F2 Exacerbates IFN-beta Expression of Human Respiratory Epithelial Cells." Journal of Immunology (Baltimore, Md. : 1950), vol. 185, no. 8, 2010, pp. 4812-23.
Le Goffic R, Bouguyon E, Chevalier C, et al. Influenza A virus protein PB1-F2 exacerbates IFN-beta expression of human respiratory epithelial cells. J Immunol. 2010;185(8):4812-23.
Le Goffic, R., Bouguyon, E., Chevalier, C., Vidic, J., Da Costa, B., Leymarie, O., ... Delmas, B. (2010). Influenza A virus protein PB1-F2 exacerbates IFN-beta expression of human respiratory epithelial cells. Journal of Immunology (Baltimore, Md. : 1950), 185(8), pp. 4812-23. doi:10.4049/jimmunol.0903952.
Le Goffic R, et al. Influenza a Virus Protein PB1-F2 Exacerbates IFN-beta Expression of Human Respiratory Epithelial Cells. J Immunol. 2010 Oct 15;185(8):4812-23. PubMed PMID: 20844191.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influenza A virus protein PB1-F2 exacerbates IFN-beta expression of human respiratory epithelial cells. AU - Le Goffic,Ronan, AU - Bouguyon,Edwige, AU - Chevalier,Christophe, AU - Vidic,Jasmina, AU - Da Costa,Bruno, AU - Leymarie,Olivier, AU - Bourdieu,Christiane, AU - Decamps,Laure, AU - Dhorne-Pollet,Sophie, AU - Delmas,Bernard, Y1 - 2010/09/15/ PY - 2010/9/17/entrez PY - 2010/9/17/pubmed PY - 2010/11/5/medline SP - 4812 EP - 23 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 185 IS - 8 N2 - 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. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/20844191/Influenza_A_virus_protein_PB1_F2_exacerbates_IFN_beta_expression_of_human_respiratory_epithelial_cells_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=20844191 DB - PRIME DP - Unbound Medicine ER -