title: Mapping the architecture of the HIV-1 Tat circuit: A decision-making circuit that lacks bistability and exploits stochastic noise.
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.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive #0314, La Jolla, CA 92093-0314, USA.
authors.forename: Brandon S
authors.initials: BS
authors.lastname: Razooky
authors.forename: Leor S
authors.initials: LS
authors.lastname: Weinberger
mesh_terms: D002460:Cell Line; D003198:Computer Simulation; D025461:Feedback, Physiological; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008954:Models, Biological; D013269:Stochastic Processes; D059008:Time-Lapse Imaging; D014158:Transcription, Genetic; D017735:Virus Latency; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D054322:tat Gene Products, Human Immunodeficiency Virus