西亚试剂：An Endogenous Accelerator for Viral Gene Expression Confers

An Endogenous Accelerator for Viral Gene Expression Confers a Fitness Advantage

Melissa W. Teng, Cynthia Bolovan-Fritts, Roy D. Dar, Andrew Womack, Michael L. Simpson, Thomas Shenk, Leor S. Weinberger

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 viruss 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.

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