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Vaccinia virus inhibits NF-κB-dependent gene expression downstream of p65 translocation

Sumner, RP, Maluquer de Motes, C, Veyer, DL and Smith, GL (2013) Vaccinia virus inhibits NF-κB-dependent gene expression downstream of p65 translocation J Virol.

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The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factor plays a critical role in host defence against viral infection by inducing the production of pro-inflammatory mediators and type I interferon. Consequently, viruses have evolved many mechanisms to block its activation. The poxvirus vaccinia virus (VACV) encodes numerous inhibitors of NF-κB activation that target multiple points in the signaling pathway. A derivative of VACV strain Copenhagen, called vv811, lacking 55 open reading frames in the left and right terminal regions of the genome, was reported to still inhibit NF-κB activation downstream of tumour necrosis factor (TNF)α and interleukin (IL)-1β, suggesting the presence of one or more additional inhibitors. In this study we constructed a recombinant vv811 lacking the recently described NF-κB inhibitor A49 (vv811ΔA49), yielding a virus that lacked all currently described inhibitors downstream of TNFα/IL-1β. Unlike vv811, vv811ΔA49 no longer inhibited degradation of phosphorylated IκBα and p65 translocated into the nucleus. However, despite this translocation, vv811ΔA49 still inhibited TNFα- and IL1β-induced NF-κB-dependent reporter gene expression and the transcription and production of cytokines induced by these agonists. This inhibition did not require late viral gene expression. These findings indicate the presence of another inhibitor of NF-κB that is expressed early during infection and acts by a novel mechanism downstream of p65 translocation into the nucleus.

Item Type: Article
Divisions : Surrey research (other units)
Authors :
Sumner, RP
Maluquer de Motes,
Veyer, DL
Smith, GL
Date : 26 December 2013
DOI : 10.1128/JVI.02627-13
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:04
Last Modified : 24 Jan 2020 18:25

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