Journal
VIROLOGY
Volume 353, Issue 1, Pages 155-165Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2006.05.022
Keywords
RSV; airway epithelial cells; IRF; ROS; inflammation
Categories
Funding
- NIAID NIH HHS [AI 01763] Funding Source: Medline
- NIEHS NIH HHS [T32 ES07254, P30ES0 6676] Funding Source: Medline
- NIGMS NIH HHS [F31 GM072231-01] Funding Source: Medline
- PHS HHS [P01 62885] Funding Source: Medline
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Respiratory syncytial virus (RSV)-induced chemokine gene expression occurs through the activation of a subset of transcription factors, including Interferon Regulatory Factor (IRF)-3. In this study, we have investigated the signaling pathway leading to RSV-induced IRF-3 activation and whether it is mediated by intracellular reactive oxygen species (ROS) generation. Our results show that RSV infection induces expression and catalytic activity of IKK epsilon, a noncanonical IKK-like kinase. Expression of a kinase-inactive IKK epsilon blocks RSV-induced IRF-3 serine phosphorylation, nuclear translocation and DNA-binding, leading to inhibition of RANTES gene transcription, mRNA expression and protein synthesis. Treatment of alveolar epithelial cells with antioxidants or with NAD(P)H oxidase inhibitors abrogates RSV-induced chemokine secretion, IRF-3 phosphorylation and IKK epsilon induction, indicating that ROS generation plays a fundamental role in the signaling pathway leading to IRF-3 activation, therefore, identifying a novel molecular target for the development of strategies aimed to modify the inflammatory response associated with RSV infection of the lung. (c) 2006 Elsevier Inc. All rights reserved.
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