Transcriptional circuit architectures in several organisms have been evolutionarily selected to dictate precise given responses. Unlike these cellular systems, HIV is regulated through a complex circuit composed of two successive phases (host and viral), which create a positive feedback loop facilitating viral replication. However, it has long remained unclear whether both phases operate identically and to what extent the host phase influences the entire circuit. Here, we report that, although the host phase is regulated by a checkpoint whereby KAP1 mediates transcription activation, the virus evolved a minimalist system bypassing KAP1. Given the complex circuit's architecture, cell-to-cell KAP1 fluctuations impart heterogeneity in the host transcriptional responses, thus affecting the feedback loop. Mathematical modeling of a complete circuit reveals how these oscillations ultimately influence homogeneous reactivation potential of a latent virus. Thus, although HIV drives molecular innovation to fuel robust gene activation, it experiences transcriptional fragility, thereby influencing viral fate and cure efforts.
Pubmed ID: 30943398 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
NIH HIV Reagent Program has been managed under contract by American Type Culture Collection (ATCC) since 2020. ATCC shall maintain the NIH HIV Reagent Program through identification, acquisition, production, receipt, storage, maintenance, distribution and disposal of biological and chemical research organisms and materials for HIV and other infectious diseases for use in basic and translational research.
View all literature mentionsThis polyclonal targets Cdk9 (C-20)
View all literature mentionsThis unknown targets mouse-IgG-control
View all literature mentionsThis polyclonal targets Goat Human IL-12 (Interleukin 12)
View all literature mentionsThis polyclonal targets RELA
View all literature mentionsThis polyclonal targets Rabbit Human IL-4 (Interleukin 4)
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis polyclonal targets Rabbit IgG
View all literature mentionsThis monoclonal targets KAP1
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis polyclonal targets Mouse IgG
View all literature mentionsThis polyclonal targets POLR2A
View all literature mentionsThis monoclonal targets CD184 (CXCR4)
View all literature mentionsCell line J-Lat 10.6 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsSoftware development environment that helps users build containerized software using Docker and Kubernetes softwares. It is executable on desktop and cloud, and allows access to a vast library of community containerized content in Docker Hub.
View all literature mentionsCell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsCell line J-Lat 6.3 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SUP-T1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line J-Lat 9.2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsDatabase of physiological, pharmacological, and pathological information on humans and other organisms and integration through computational modeling. Models include everything from diagrammatic schema, suggesting relationships among elements composing a system, to fully quantitative, computational models describing the behavior of physiological systems and an organism''s response to environmental change. Each mathematical model is an internally self-consistent summary of available information, and thereby defines a working hypothesis about how a system operates. Predictions from such models are subject to test, with new results leading to new models.BR /> A Tool developed for the NSR Physiome project is JSim, an open source, free software. JSim is a Java-based simulation system for building quantitative numeric models and analyzing them with respect to experimental reference data. JSim''s primary focus is in physiology and biomedicine, however its computational engine is quite general and applicable to a wide range of scientific domains. JSim models may intermix ODEs, PDEs, implicit equations, integrals, summations, discrete events and procedural code as appropriate. JSim''s model compiler can automatically insert conversion factors for compatible physical units as well as detect and reject unit unbalanced equations. JSim also imports the SBML and CellML model archival formats. All JSim models are open source. Goals of the Physiome Project: - To develop and database observations of physiological phenomenon and interpret these in terms of mechanism (a fundamentally reductionist goal). - To integrate experimental information into quantitative descriptions of the functioning of humans and other organisms (modern integrative biology glued together via modeling). - To disseminate experimental data and integrative models for teaching and research. - To foster collaboration amongst investigators worldwide, to speed up the discovery of how biological systems work. - To determine the most effective targets (molecules or systems) for therapy, either pharmaceutic or genomic. - To provide information for the design of tissue-engineered, biocompatible implants.
View all literature mentionsCell line J-Lat 8.4 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Jurkat E6.1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsA collection of tools for flow cytometer and application setup, data acquisition, and data analysis that help streamline flow cytometry workflows. It provides features to help users integrate flow systems into new application areas, including index sorting for stem cell and single-cell applications, as well as automation protocols for high-throughput and robotic laboratories.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsCell line HEK293T/17 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsThis polyclonal targets Rabbit Human IL-4 (Interleukin 4)
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsCell line J-Lat 9.2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line J-Lat 8.4 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line J-Lat 6.3 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T/17 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SUP-T1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Jurkat E6.1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line J-Lat 10.6 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsA collection of tools for flow cytometer and application setup, data acquisition, and data analysis that help streamline flow cytometry workflows. It provides features to help users integrate flow systems into new application areas, including index sorting for stem cell and single-cell applications, as well as automation protocols for high-throughput and robotic laboratories.
View all literature mentionsSoftware development environment that helps users build containerized software using Docker and Kubernetes softwares. It is executable on desktop and cloud, and allows access to a vast library of community containerized content in Docker Hub.
View all literature mentionsDatabase of physiological, pharmacological, and pathological information on humans and other organisms and integration through computational modeling. Models include everything from diagrammatic schema, suggesting relationships among elements composing a system, to fully quantitative, computational models describing the behavior of physiological systems and an organism''s response to environmental change. Each mathematical model is an internally self-consistent summary of available information, and thereby defines a working hypothesis about how a system operates. Predictions from such models are subject to test, with new results leading to new models.BR /> A Tool developed for the NSR Physiome project is JSim, an open source, free software. JSim is a Java-based simulation system for building quantitative numeric models and analyzing them with respect to experimental reference data. JSim''s primary focus is in physiology and biomedicine, however its computational engine is quite general and applicable to a wide range of scientific domains. JSim models may intermix ODEs, PDEs, implicit equations, integrals, summations, discrete events and procedural code as appropriate. JSim''s model compiler can automatically insert conversion factors for compatible physical units as well as detect and reject unit unbalanced equations. JSim also imports the SBML and CellML model archival formats. All JSim models are open source. Goals of the Physiome Project: - To develop and database observations of physiological phenomenon and interpret these in terms of mechanism (a fundamentally reductionist goal). - To integrate experimental information into quantitative descriptions of the functioning of humans and other organisms (modern integrative biology glued together via modeling). - To disseminate experimental data and integrative models for teaching and research. - To foster collaboration amongst investigators worldwide, to speed up the discovery of how biological systems work. - To determine the most effective targets (molecules or systems) for therapy, either pharmaceutic or genomic. - To provide information for the design of tissue-engineered, biocompatible implants.
View all literature mentionsThis polyclonal targets Mouse IgG
View all literature mentionsThis polyclonal targets Rabbit IgG
View all literature mentionsThis unknown targets mouse-IgG-control
View all literature mentionsThis polyclonal targets Goat Human IL-12 (Interleukin 12)
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD184 (CXCR4)
View all literature mentionsThis polyclonal targets RELA
View all literature mentionsThis polyclonal targets Cdk9 (C-20)
View all literature mentionsThis polyclonal targets POLR2A
View all literature mentionsThis monoclonal targets KAP1
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentions