Human cytomegalovirus IE86 attenuates virus- and tumor necrosis factor alpha-induced NFκB-dependent gene expression

R. Travis Taylor, Wade A. Bresnahan

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Human cytomegalovirus (HCMV) infection regulates a number of genes involved in the host antiviral response. We have previously reported that HCMV attenuates the expression of beta Interferon (IFN-β) and a number of proinflammatory chemokines, and this attenuation is mediated by the HCMV immediate-early protein IE86. The present study seeks to identify the mechanism by which IE86 blocks IFN-β expression. We demonstrate that the induction of IFN-β during HCMV infection requires the activation of both the IRF-3 and the NFκB pathways. Therefore, IE86 may target either pathway to block IFN-β expression. Our results show that IE86 does not block IRF-3 phosphorylation, dimerization, nuclear translocation, or target gene expression. However, using gel shift analysis, we demonstrate that IE86 efficiently inhibits virus-induced binding of NFκB to the IFN-β promoter, resulting in attenuation of IFN-β and NFκB-dependent gene expression. Furthermore, IE86 expression inhibits tumor necrosis factor alpha-induced NFκB DNA binding and target gene expression. Together, these results identify IE86 as a NFκB antagonist, which results in the suppression of NFκB-dependent cytokine and chemokine gene expression.

Original languageEnglish (US)
Pages (from-to)10763-10771
Number of pages9
JournalJournal of virology
Volume80
Issue number21
DOIs
StatePublished - Nov 2006

Bibliographical note

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

Fingerprint Dive into the research topics of 'Human cytomegalovirus IE86 attenuates virus- and tumor necrosis factor alpha-induced NFκB-dependent gene expression'. Together they form a unique fingerprint.

Cite this