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

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

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Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive #0314, La Jolla, CA 92093-0314, USA.


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.

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