Dataset Information

3D Spatially Resolved Models of the Intracellular Dynamics of the Hepatitis C Genome Replication Cycle.

ABSTRACT: Mathematical models of virus dynamics have not previously acknowledged spatial resolution at the intracellular level despite substantial arguments that favor the consideration of intracellular spatial dependence. The replication of the hepatitis C virus (HCV) viral RNA (vRNA) occurs within special replication complexes formed from membranes derived from endoplasmatic reticulum (ER). These regions, termed membranous webs, are generated primarily through specific interactions between nonstructural virus-encoded proteins (NSPs) and host cellular factors. The NSPs are responsible for the replication of the vRNA and their movement is restricted to the ER surface. Therefore, in this study we developed fully spatio-temporal resolved models of the vRNA replication cycle of HCV. Our simulations are performed upon realistic reconstructed cell structures-namely the ER surface and the membranous webs-based on data derived from immunostained cells replicating HCV vRNA. We visualized 3D simulations that reproduced dynamics resulting from interplay of the different components of our models (vRNA, NSPs, and a host factor), and we present an evaluation of the concentrations for the components within different regions of the cell. Thus far, our model is restricted to an internal portion of a hepatocyte and is qualitative more than quantitative. For a quantitative adaption to complete cells, various additional parameters will have to be determined through further in vitro cell biology experiments, which can be stimulated by the results deccribed in the present study.

SUBMITTER: Knodel MM

PROVIDER: S-EPMC5691296 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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3D Spatially Resolved Models of the Intracellular Dynamics of the Hepatitis C Genome Replication Cycle.

Knodel Markus M MM Reiter Sebastian S Targett-Adams Paul P Grillo Alfio A Herrmann Eva E Wittum Gabriel G

Viruses 20170930 10

Mathematical models of virus dynamics have not previously acknowledged spatial resolution at the intracellular level despite substantial arguments that favor the consideration of intracellular spatial dependence. The replication of the hepatitis C virus (HCV) viral RNA (vRNA) occurs within special replication complexes formed from membranes derived from endoplasmatic reticulum (ER). These regions, termed membranous webs, are generated primarily through specific interactions between nonstructural ...[more]

PMID: 28973992

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Project description:PurposePrior versions of the Tool for Reduction and Assessment of Chemical and other environmental Impacts (TRACI) have recognized the need for spatial variability when characterizing eutrophication. However, the method's underlying environmental models had not been updated to reflect the latest science. This new research provides the ability to differentiate locations with a high level of detail within the USA and provides global values at the country level.MethodsIn previous research (Morelli et al. 2018), the authors reviewed a broad range of domain-specific models and life cycle assessment methods for characterization of eutrophication and ranked these by levels of importance to the field and readiness for further development. The current research is rooted in the decision outcome of Morelli et al. (2018) to separate freshwater and marine eutrophication to allow for the most tailored characterization of each category individually. The current research also assumes that freshwater systems are limited by phosphorus and marine systems are limited by nitrogen. Using a combination of spatial modeling methods for soil, air, and water, we calculate midpoint characterization factors for freshwater and marine eutrophication categories and evaluate the results through a US-based case application.Results and discussionMaps of the nutrient inventories, characterization factors, and overall impacts of the case application illustrate the spatial variation and patterns in the results. The importance of variation in geographic location is demonstrated using nutrient-based activity likelihood categories of agricultural (rural fertilizer), non-agricultural (urban fertilizer), and general (human waste processing). Proximity to large bodies of water, as well as individual hydraulic residence times, was shown to affect the comparative values of characterization factors across the USA.ConclusionsIn this paper, we have calculated and applied finely resolved freshwater and marine eutrophication characterization factors for the USA and country-level factors for the rest of the globe. Additional research is needed to provide similarly resolved characterization factors for the entire globe, which would require expansion of publicly available data and further development of applicable fate and transport models. Further scientific advances may also be considered as computing capabilities become more sophisticated and widely accessible.

Dataset Information

3D Spatially Resolved Models of the Intracellular Dynamics of the Hepatitis C Genome Replication Cycle.

Publications

3D Spatially Resolved Models of the Intracellular Dynamics of the Hepatitis C Genome Replication Cycle.

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