Identification of TRIM23 As a Cofactor Involved in the Regulation of NF-kappaB by Human Cytomegalovirus

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2009 Jan 30

PMID 19176615

Citations 47

Authors

Emma Poole

Ian Groves

Andrew MacDonald

Yin Pang

Antonio Alcami

John Sinclair

Affiliations

Soon will be listed here.

Abstract

Human cytomegalovirus (HCMV) regulates NF-kappaB during infection by a variety of mechanisms. For example, the HCMV gene product, UL144, is known to activate NF-kappaB 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-kappaB by UL144 is dependent upon cellular tripartite motif 23 (TRIM23) protein. We propose a mechanism by which UL144 activates NF-kappaB 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-kappaB. Therefore, we present a novel role for TRIM23 that is specific to UL144-mediated activation of NF-kappaB during the course of virus infection.

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