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Journal of Virology, April 2009, p. 3581-3590, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.02072-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Identification of TRIM23 as a Cofactor Involved in the Regulation of NF-{kappa}B by Human Cytomegalovirus{triangledown}

Emma Poole,1 Ian Groves,1 Andrew Macdonald,3 Yin Pang,1 Antonio Alcami,1,2 and John Sinclair1*

Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, United Kingdom,1 Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), 28049 Madrid, Spain,2 Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom3

Received 2 October 2008/ Accepted 15 January 2009

Human cytomegalovirus (HCMV) regulates NF-{kappa}B during infection by a variety of mechanisms. For example, the HCMV gene product, UL144, is known to activate NF-{kappa}B in a tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6)-dependent manner, causing the upregulation of the chemokine CCL22 (MDC). Viral UL144 is expressed from the UL/b' region of the HCMV genome at early times postinfection and is a TNFR1-like homologue. Despite this homology to the TNFR1 receptor superfamily, UL144 does not bind to members of the TNF ligand superfamily. We show here that the upregulation of NF-{kappa}B by UL144 is dependent upon cellular tripartite motif 23 (TRIM23) protein. We propose a mechanism by which UL144 activates NF-{kappa}B through a direct interaction with the cellular protein TRIM23 in a complex containing TRAF6. In contrast, TRIM23 is not involved in conventional double-stranded RNA signaling via NF-{kappa}B. Therefore, we present a novel role for TRIM23 that is specific to UL144-mediated activation of NF-{kappa}B during the course of virus infection.


* Corresponding author. Mailing address: University of Cambridge, Department of Medicine, Box 157, Level 5, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, United Kingdom. Phone: 441223-336860. Fax: 441223-336846. E-mail: js{at}mole.bio.cam.ac.uk

{triangledown} Published ahead of print on 28 January 2009.


Journal of Virology, April 2009, p. 3581-3590, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.02072-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.