ArticlePLoS biology2007
An HIV feedback resistor: auto-regulatory circuit deactivator and noise buffer.
Article in PLoS biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 94 citations in OpenAlex.
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- The influence of HIV sense and antisense transcripts on stochastic HIV transcription and reactivation.Computational and structural biotechnology journal · 2025Article
- CDK8 inhibitors antagonize HIV-1 reactivation and promote provirus latency in T cells.Journal of virology · 2023Article
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- Origin and functional role of antisense transcription in endogenous and exogenous retroviruses.Retrovirology · 2023Review
- Enhanced Transcriptional Strength of HIV-1 Subtype C Minimizes Gene Expression Noise and Confers Stability to the Viral Latent State.Journal of virology · 2023Article
- TRIM24 controls induction of latent HIV-1 by stimulating transcriptional elongation.Communications biology · 2023Article
- The nonequilibrium mechanism of noise-enhanced drug synergy in HIV latency reactivation.iScience · 2022Article
- ZBTB2 represses HIV-1 transcription and is regulated by HIV-1 Vpr and cellular DNA damage responses.PLoS pathogens · 2021Article
- A Stronger Transcription Regulatory Circuit of HIV-1C Drives the Rapid Establishment of Latency with Implications for the Direct Involvement of Tat.Journal of virology · 2020Article
- Trade-off between synergy and efficacy in combinations of HIV-1 latency-reversing agents.PLoS computational biology · 2018Article
- Dynamics of the Gene Regulatory Network of HIV-1 and the Role of Viral Non-coding RNAs on Latency Reversion.Frontiers in physiology · 2018Article
- Nonlatching positive feedback enables robust bimodality by decoupling expression noise from the mean.PLoS biology · 2017Article
- Fate-Regulating Circuits in Viruses: From Discovery to New Therapy Targets.Annual review of virology · 2017Review
- Transient Thresholding: A Mechanism Enabling Noncooperative Transcriptional Circuitry to Form a Switch.Biophysical journal · 2017Article
- Distinct promoter activation mechanisms modulate noise-driven HIV gene expression.Scientific reports · 2015Article
- Effects of promoter leakage on dynamics of gene expression.BMC systems biology · 2015Article
- A hardwired HIV latency program.Cell · 2015Article
- Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
Animal viruses (e.g., lentiviruses and herpesviruses) use transcriptional positive feedback (i.e., transactivation) to regulate their gene expression. But positive-feedback circuits are inherently unstable when turned off, which presents a particular dilemma for latent viruses that lack transcriptional repressor motifs. Here we show that a dissipative feedback resistor, composed of enzymatic interconversion of the transactivator, converts transactivation circuits into excitable systems that generate transient pulses of expression, which decay to zero. We use HIV-1 as a model system and analyze single-cell expression kinetics to explore whether the HIV-1 transactivator of transcription (Tat) uses a resistor to shut off transactivation. The Tat feedback circuit was found to lack bi-stability and Tat self-cooperativity but exhibited a pulse of activity upon transactivation, all in agreement with the feedback resistor model. Guided by a mathematical model, biochemical and genetic perturbation of the suspected Tat feedback resistor altered the circuit's stability and reduced susceptibility to molecular noise, in agreement with model predictions. We propose that the feedback resistor is a necessary, but possibly not sufficient, condition for turning off noisy transactivation circuits lacking a repressor motif (e.g., HIV-1 Tat). Feedback resistors may be a paradigm for examining other auto-regulatory circuits and may inform upon how viral latency is established, maintained, and broken.
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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.