title: NF-kappaB-dependent induction of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas/FasL is crucial for efficient influenza virus propagation.
abstract: Activation of the transcription factor NF-kappaB is a hallmark of infections by viral pathogens including influenza viruses. Because gene expression of many proinflammatory and antiviral cytokines is controlled by this factor, the concept emerged that NF-kappaB and its upstream regulator IkappaB kinase are essential components of the innate antiviral immune response to infectious pathogens. In contrast to this common view we report here that NF-kappaB activity promotes efficient influenza virus production. On a molecular level this is due to NF-kappaB-dependent viral induction of the proapoptotic factors tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and FasL, which enhance virus propagation in an autocrine and paracrine fashion. Thus, NF-kappaB acts both proapoptotically and provirally in the context of an influenza virus infection.
authors.affiliation: Institute of Molecular Medicine, Heinrich-Heine Universität, Universitätsstrasse 1, D-40225 Düsseldorf, Germany.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Wurzer
authors.forename: Christina
authors.initials: C
authors.lastname: Ehrhardt
authors.forename: Stephan
authors.initials: S
authors.lastname: Pleschka
authors.forename: Friederike
authors.initials: F
authors.lastname: Berberich-Siebelt
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wolff
authors.forename: Henning
authors.initials: H
authors.lastname: Walczak
authors.forename: Oliver
authors.initials: O
authors.lastname: Planz
authors.forename: Stephan
authors.initials: S
authors.lastname: Ludwig
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002460:Cell Line; D002522:Chlorocebus aethiops; D004285:Dogs; D053222:Fas Ligand Protein; D006801:Humans; D051550:I-kappa B Kinase; D009980:Influenza A virus / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014709:Vero Cells; D014779:Virus Replication; D019014:fas Receptor / Q000096:biosynthesis*
chemical_list: D051017:Apoptosis Regulatory Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human