IKKε modulates RSV-induced NF-κB-dependent gene transcription.
Respiratory syncytial virus (RSV), a negative-strand RNA virus, is the most common cause of epidemic respiratory disease in infants and young children. RSV infection of airway epithelial cells induces the expression of immune/inflammatory genes through the activation of a subset of transcription factors, including Nuclear Factor-κB (NF-κB). In this study we have investigated the role of the non canonical IκB kinase (IKK)ε in modulating RSV-induced NF-κB activation. Our results show that inhibition of IKKε activation results in significant impairment of viral-induced NF-κB-dependent gene expression, through a reduction in NF-κB transcriptional activity, without changes in nuclear translocation or DNA-binding activity. Absence of IKKε results in a significant decrease of RSV-induced NF-κB phosphorylation on serine 536, a post-translational modification important for RSV-induced NF-κB-dependent gene expression, known to regulate NF-κB transcriptional activity without affecting nuclear translocation. This study identifies a novel mechanism by which IKKε regulates viral-induced cellular signaling.
Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.
Xiaoyong
X
Bao
Hemalatha
H
Indukuri
Tianshuang
T
Liu
Sui-Ling
SL
Liao
Bing
B
Tian
Allan R
AR
Brasier
Roberto P
RP
Garofalo
Antonella
A
Casola
D000818:Animals; D002460:Cell Line; D006801:Humans; D051550:I-kappa B Kinase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000472:pathogenicity*; D051996:Transcription Factor RelA / Q000378:metabolism; D014158:Transcription, Genetic
C508606:CXCL8 protein, human; D016209:Interleukin-8; D016328:NF-kappa B; C498143:RELA protein, human; D051996:Transcription Factor RelA; D051550:I-kappa B Kinase