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

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Details zur Publikation

Autorinnen und Autoren: Knodel M
Zeitschrift: Viruses-Basel
Verlag: MDPI AG
Jahr der Veröffentlichung: 2017
Band: 9
Heftnummer: 10
ISSN: 1999-4915


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 structuresnamely the ER surface and the membranous websbased 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 described in the present study.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Knodel, Markus Dr.
Lehrstuhl für Angewandte Mathematik (Modellierung und Numerik)

Zuletzt aktualisiert 2018-12-11 um 10:53