Defective NF-kappaB activation in virus-infected neuronal cells is restored by genetic complementation.
The interferon-beta (IFNbeta) gene is not inducible in neuronal cells in response to measles virus (MV) due to lack of nuclear factor kappa B (NF-kappaB) activation. NF-kappaB is normally sequestered in the cytoplasm by an inhibitor (IkappaBalpha). Previously, the authors demonstrated that the failure to activate neuronal NF-kappaB by MV was due to the inability to phosphorylate and degrade its inhibitor, IkappaBalpha. Here the authors demonstrate that transient transfection of a brain cDNA library into neuronal cells restores the ability of MV to activate NF-kappaB. In addition, tumor necrosis factor-alpha (TNFalpha), but not interleukin-1 (IL-1) or lipopolysaccharide (LPS), stimulation resulted in IkappaBalpha phosphorylation and degradation in two neuronal cell lines. These results indicate that failure of MV to activate neuronal NF-kappaB is due to a signaling defect and that MV utilizes an NF-kappaB signaling pathway distinct from that of TNFalpha, but may overlap with that for IL-1 and LPS.
Fang
Yu-Yan
YY
Department of Neurology, University of Maryland at Baltimore, and Department of Veterans Affairs, Baltimore, Maryland, USA.
Song
Zan-Min
ZM
Wu
Tao
T
Raha
Abhijit
A
Kalvakolanu
Dhananjaya V
DV
Dhib-Jalbut
Suhayl
S
D002460:Cell Line; D015723:Gene Library; D005816:Genetic Complementation Test; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016899:Interferon-beta / Q000494:pharmacology; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008459:Measles virus; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism / Q000821:virology*; D009474:Neurons / Q000378:metabolism / Q000821:virology*; D010766:Phosphorylation; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha
D020672:I-kappa B Proteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D016899:Interferon-beta