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-kappa B (NF-kappa B). In this study we have investigated the role of the non canonical I kappa B kinase (IKK)epsilon in modulating RSV-induced NF-kappa B activation. Our results show that inhibition of IKK epsilon activation results in significant impairment of viral-induced NF-kappa B-dependent gene expression, through a reduction in NF-kappa B transcriptional activity, without changes in nuclear translocation or DNA-binding activity. Absence of IKK epsilon results in a significant decrease of RSV-induced NF-kappa B phosphorylation on serine 536, a post-translational modification important for RSV-induced NF-kappa B-dependent gene expression, known to regulate NF-kappa B transcriptional activity without affecting nuclear translocation. This study identifies a novel mechanism by which IKK epsilon regulates viral-induced cellular signaling. (C) 2010 Elsevier Inc. All rights reserved.