NF-kappaB-dependent induction of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas/FasL is crucial for efficient influenza virus propagation.
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.
Wurzer
Walter J
WJ
Institute of Molecular Medicine, Heinrich-Heine Universität, Universitätsstrasse 1, D-40225 Düsseldorf, Germany.
Ehrhardt
Christina
C
Pleschka
Stephan
S
Berberich-Siebelt
Friederike
F
Wolff
Thorsten
T
Walczak
Henning
H
Planz
Oliver
O
Ludwig
Stephan
S
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*
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