TY  - JOUR
A1  - Knodel, Markus Michael
A1  - Targett-Adams, Paul
A1  - Grillo, Alfio
A1  - Herrmann, Eva
A1  - Wittum, Gabriel
T1  - Advanced hepatitis C virus replication PDE models within a realistic intracellular geometric environment
T2  - International journal of environmental research and public health
N2  - The hepatitis C virus (HCV) RNA replication cycle is a dynamic intracellular process occurring in three-dimensional space (3D), which is difficult both to capture experimentally and to visualize conceptually. HCV-generated replication factories are housed within virus-induced intracellular structures termed membranous webs (MW), which are derived from the Endoplasmatic Reticulum (ER). Recently, we published 3D spatiotemporal resolved diffusion–reaction models of the HCV RNA replication cycle by means of surface partial differential equation (sPDE) descriptions. We distinguished between the basic components of the HCV RNA replication cycle, namely HCV RNA, non-structural viral proteins (NSPs), and a host factor. In particular, we evaluated the sPDE models upon realistic reconstructed intracellular compartments (ER/MW). In this paper, we propose a significant extension of the model based upon two additional parameters: different aggregate states of HCV RNA and NSPs, and population dynamics inspired diffusion and reaction coefficients instead of multilinear ones. The combination of both aspects enables realistic modeling of viral replication at all scales. Specifically, we describe a replication complex state consisting of HCV RNA together with a defined amount of NSPs. As a result of the combination of spatial resolution and different aggregate states, the new model mimics a cis requirement for HCV RNA replication. We used heuristic parameters for our simulations, which were run only on a subsection of the ER. Nevertheless, this was sufficient to allow the fitting of core aspects of virus reproduction, at least qualitatively. Our findings should help stimulate new model approaches and experimental directions for virology.
KW  - computational virology
KW  - hepatitis C virus (HCV)
KW  - viral dynamics
KW  - within-host viral modeling
KW  - mathematical models of viral RNA cycle
KW  - population dynamics
KW  - 3D spatiotemporal resolved mathematical models
KW  - realistic geometries
KW  - (surface) partial differential equations
KW  - Finite Volumes
KW  - massively parallel multigrid solvers
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/49142
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-491425
SN  - 1660-4601
SN  - 1661-7827
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  - 16
IS  - 3, Art. 513
SP  - 1
EP  - 53
PB  - MDPI AG
CY  - Basel
ER  -