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Journal of Virology, November 2006, p. 10763-10771, Vol. 80, No. 21
0022-538X/06/$08.00+0     doi:10.1128/JVI.01195-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Human Cytomegalovirus IE86 Attenuates Virus- and Tumor Necrosis Factor Alpha-Induced NF{kappa}B-Dependent Gene Expression

R. Travis Taylor{dagger} and Wade A. Bresnahan*

Department of Microbiology, University of Minnesota, 1060 Mayo Building, MMC196, Minneapolis, Minnesota 55455

Received 6 June 2006/ Accepted 9 August 2006

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-ß) 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-ß expression. We demonstrate that the induction of IFN-ß during HCMV infection requires the activation of both the IRF-3 and the NF{kappa}B pathways. Therefore, IE86 may target either pathway to block IFN-ß 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 NF{kappa}B to the IFN-ß promoter, resulting in attenuation of IFN-ß and NF{kappa}B-dependent gene expression. Furthermore, IE86 expression inhibits tumor necrosis factor alpha-induced NF{kappa}B DNA binding and target gene expression. Together, these results identify IE86 as a NF{kappa}B antagonist, which results in the suppression of NF{kappa}B-dependent cytokine and chemokine gene expression.

* Corresponding author. Mailing address: University of Minnesota, Department of Microbiology, 1060 Mayo Building, MMC196, 420 Delaware Street SE, Minneapolis, MN 55455. Phone: (612) 626-5876. Fax: (612) 626-0623. E-mail: bresn013{at}umn.edu.

{dagger} Present address: UT Southwestern Medical Center, Department of Microbiology, 6000 Harry Hines Blvd, Dallas, TX 75390.

Journal of Virology, November 2006, p. 10763-10771, Vol. 80, No. 21
0022-538X/06/$08.00+0     doi:10.1128/JVI.01195-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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