Mapping the architecture of the HIV-1 Tat circuit: A decision-making circuit that lacks bistability and exploits stochastic noise

Methods. 2011 Jan;53(1):68-77. doi: 10.1016/j.ymeth.2010.12.006. Epub 2010 Dec 16.

Abstract

Upon infection of a CD4(+) T cell, HIV-1 appears to 'choose' between two alternate fates: active replication or a long-lived dormant state termed proviral latency. A transcriptional positive-feedback loop generated by the HIV-1 Tat protein appears sufficient to mediate this decision. Here, we describe a coupled wet-lab and computational approach that uses mathematical modeling and live-cell time-lapse microscopy to map the architecture of the HIV-1 Tat transcriptional regulatory circuit and generate predictive models of HIV-1 latency. This approach provided the first characterization of a 'decision-making' circuit that lacks bistability and instead exploits stochastic fluctuations in cellular molecules (i.e. noise) to generate a decision between an on or off transcriptional state.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Line
  • Computer Simulation
  • Feedback, Physiological*
  • Gene Expression Regulation, Viral*
  • Genetic Vectors
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Humans
  • Lentivirus / genetics
  • Models, Biological
  • Stochastic Processes
  • Time-Lapse Imaging
  • Transcription, Genetic*
  • Virus Latency
  • tat Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • tat Gene Products, Human Immunodeficiency Virus