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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Apoptosis Regulatory Proteins
-
Cell Line
-
Chlorocebus aethiops
-
Dogs
-
Fas Ligand Protein
-
Humans
-
I-kappa B Kinase
-
Influenza A virus / physiology*
-
Membrane Glycoproteins / biosynthesis*
-
Mutation
-
NF-kappa B / metabolism*
-
Protein Serine-Threonine Kinases / genetics
-
Protein Serine-Threonine Kinases / metabolism
-
Signal Transduction
-
TNF-Related Apoptosis-Inducing Ligand
-
Tumor Necrosis Factor-alpha / biosynthesis*
-
Vero Cells
-
Virus Replication
-
fas Receptor / biosynthesis*
Substances
-
Apoptosis Regulatory Proteins
-
FASLG protein, human
-
Fas Ligand Protein
-
Membrane Glycoproteins
-
NF-kappa B
-
TNF-Related Apoptosis-Inducing Ligand
-
TNFSF10 protein, human
-
Tumor Necrosis Factor-alpha
-
fas Receptor
-
Protein Serine-Threonine Kinases
-
CHUK protein, human
-
I-kappa B Kinase
-
IKBKB protein, human
-
IKBKE protein, human