IKKε modulates RSV-induced NF-κB-dependent gene transcription

Virology. 2010 Dec 20;408(2):224-31. doi: 10.1016/j.virol.2010.09.016. Epub 2010 Oct 18.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Humans
  • I-kappa B Kinase / deficiency
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism*
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / genetics
  • Mice
  • Mice, Knockout
  • Mutation
  • NF-kappa B / metabolism*
  • Phosphorylation
  • RNA Interference
  • Respiratory Syncytial Virus Infections / genetics
  • Respiratory Syncytial Virus Infections / metabolism
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Viruses / pathogenicity*
  • Transcription Factor RelA / metabolism
  • Transcription, Genetic*


  • CXCL8 protein, human
  • Interleukin-8
  • NF-kappa B
  • RELA protein, human
  • Transcription Factor RelA
  • I-kappa B Kinase