ArticleCell2012
An endogenous accelerator for viral gene expression confers a fitness advantage.
Article in Cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 50 citations in OpenAlex.
- Evidence for G-quadruplex-mediated transactivation by the immediate-early 2 protein of human cytomegalovirus.Journal of virology · 2025Article
- Characterization of the Ictalurid herpesvirus 1 immediate-early gene ORF24 and its potential role in transcriptional regulation in yeast.Archives of virology · 2024Article
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- Investigating N-arylpyrimidinamine (NAPA) compounds as early-stage inhibitors against human cytomegalovirus.Antiviral research · 2023Article
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- Distinct Oncogenic Transcriptomes in Human Mammary Epithelial Cells Infected With Cytomegalovirus.Frontiers in immunology · 2021Article
- Editorial: Cytomegalovirus Pathogenesis and Host Interactions.Frontiers in cellular and infection microbiology · 2021Article
- A molecular mechanism for probabilistic bet hedging and its role in viral latency.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Bright and Early: Inhibiting Human Cytomegalovirus by Targeting Major Immediate-Early Gene Expression or Protein Function.Viruses · 2020Review
- Control of Immediate Early Gene Expression for Human Cytomegalovirus Reactivation.Frontiers in cellular and infection microbiology · 2020Review
- The HSV-1 ICP4 Transcriptional Auto-Repression Circuit Functions as a Transcriptional "Accelerator" Circuit.Frontiers in cellular and infection microbiology · 2020Article
- Overcoming the Cost of Positive Autoregulation by Accelerating the Response with a Coupled Negative Feedback.Cell reports · 2018Article
- Feedback-mediated signal conversion promotes viral fitness.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- The transcriptome of human mammary epithelial cells infected with the HCMV-DB strain displays oncogenic traits.Scientific reports · 2018Article
- Article
- The Human Cytomegalovirus Strain DB Activates Oncogenic Pathways in Mammary Epithelial Cells.EBioMedicine · 2018Article
- miRNA-mediated targeting of human cytomegalovirus reveals biological host and viral targets of IE2.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- A Bioreactor Method to Generate High-titer, Genetically Stable, Clinical-isolate Human Cytomegalovirus.Bio-protocol · 2017Article
- Fate-Regulating Circuits in Viruses: From Discovery to New Therapy Targets.Annual review of virology · 2017Review
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.