TY  - JOUR
A1  - Knodel, Markus Michael
A1  - Reiter, Sebastian
A1  - Targett-Adams, Paul
A1  - Grillo, Alfio
A1  - Herrmann, Eva
A1  - Wittum, Gabriel
T1  - 3D spatially resolved models of the intracellular dynamics of the hepatitis C genome replication cycle
T2  - Viruses
N2  - 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.
KW  - computational virology
KW  - hepatitis C virus
KW  - viral dynamics
KW  - within-host viral modelling
KW  - mathematical models of viral RNA cycle
KW  - 3D spatio-temporal resolved mathematical models
KW  - realistic geometries
KW  - (surface) partial differential equations
KW  - Finite Volumes
KW  - massively parallel multigrid solvers
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/44360
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-443601
N1  - This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
VL  - 9
IS  - 282
SP  - 1
EP  - 36
PB  - MDPI
CY  - Basel
ER  -