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Cell. 2012 Dec 21;151(7):1569-80. doi: 10.1016/j.cell.2012.11.051.

An endogenous accelerator for viral gene expression confers a fitness advantage.

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1
The Gladstone Institutes, San Francisco, CA 94158, USA.

Erratum in

  • Cell. 2013 Feb 28;152(5):1195.

Abstract

Many signaling circuits face a fundamental tradeoff between accelerating their response speed while maintaining final levels below a cytotoxic threshold. Here, we describe a transcriptional circuitry that dynamically converts signaling inputs into faster rates without amplifying final equilibrium levels. Using time-lapse microscopy, we find that transcriptional activators accelerate human cytomegalovirus (CMV) gene expression in single cells without amplifying steady-state expression levels, and this acceleration generates a significant replication advantage. We map the accelerator to a highly self-cooperative transcriptional negative-feedback loop (Hill coefficient ∼7) generated by homomultimerization of the virus's essential transactivator protein IE2 at nuclear PML bodies. Eliminating the IE2-accelerator circuit reduces transcriptional strength through mislocalization of incoming viral genomes away from PML bodies and carries a heavy fitness cost. In general, accelerators may provide a mechanism for signal-transduction circuits to respond quickly to external signals without increasing steady-state levels of potentially cytotoxic molecules.

PMID:
23260143
PMCID:
PMC3552493
DOI:
10.1016/j.cell.2012.11.051
[Indexed for MEDLINE]
Free PMC Article
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