Control of taNK-binding kinase 1-mediated signaling by the γ1 34.5 protein of herpes simplex virus 1

Dustin Verpooten, Ma Yijie, Songwang Hou, Zhipeng Yan, Bin He*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

131 Scopus citations


TANK-binding kinase 1 (TBK1) is a key component of Tolllike receptor-dependent and -independent signaling pathways. In response to microbial components, TBK1 activates interferon regulatory factor 3 (IRF3) and cytokine expression. Here we show that TBK1 is a novel target of the γ 134.5 protein, a virulence factor whose expression is regulated in a temporal fashion. Remarkably, the γ134.5 protein is required to inhibit IRF3 phosphorylation, nuclear translocation, and the induction of antiviral genes in infected cells. When expressed in mammalian cells, the γ134.5 protein forms complexes with TBK1 and disrupts the interaction of TBK1 and IRF3, which prevents the induction of interferon and interferon-stimulated gene promoters. Down-regulation of TBK1 requires the amino-terminal domain. In addition, unlike wild type virus, a herpes simplex virus mutant lacking γ134.5 replicates efficiently in TBK1 -/- cells but not in TBK1+/+ cells. Addition of exogenous interferon restores the antiviral activity in both TBK1-/- and TBK+/+ cells. Hence, control of TBK1-mediated cell signaling by the γ134.5 protein contributes to herpes simplex virus infection. These results reveal that TBK1 plays a pivotal role in limiting replication of a DNA virus.

Original languageEnglish (US)
Pages (from-to)1097-1105
Number of pages9
JournalJournal of Biological Chemistry
Issue number2
StatePublished - Jan 9 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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