title: The influenza virus protein PB1-F2 interacts with IKKβ and modulates NF-κB signalling.
abstract: PB1-F2, a protein encoded by a second open reading frame of the influenza virus RNA segment 2, has emerged as a modulator of lung inflammatory responses but the molecular mechanisms underlying this are only poorly understood. Here we show that PB1-F2 inhibits the activation of NF-κB dependent signalling pathways in luciferase reporter assays. PB1-F2 proteins from four different viruses interact with IKKβ in yeast two-hybrid assays and by co-immunoprecipitation. PB1-F2 expression did not inhibit IKKβ kinase activity or NF-κB translocation into the nucleus, but NF-κB binding to DNA was severely impaired in PB1-F2 transfected cells as assessed by Electrophoretic Mobility Shift Assay. Neither the N-terminal 57 amino acid truncated forms nor the C-terminus of PB1-F2 were able to inhibit NF-κB dependent signalling, indicating that the full length protein is necessary for the inhibition.
authors.affiliation: Division of Virology, MRC National Institute for Medical Research, London, United Kingdom.
authors.forename: Ana Luísa
authors.initials: AL
authors.lastname: Reis
authors.forename: John W
authors.initials: JW
authors.lastname: McCauley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002522:Chlorocebus aethiops; D004247:DNA / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014709:Vero Cells; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; C442816:PB1-F2 protein, Influenza A virus; D014764:Viral Proteins; D004247:DNA; D051550:I-kappa B Kinase