Advanced hepatitis C virus replication PDE models within a realistic intracellular geometric environment

  • 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.

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Author:Markus Michael Knodel, Paul Targett-Adams, Alfio Grillo, Eva HerrmannORCiD, Gabriel WittumGND
URN:urn:nbn:de:hebis:30:3-491425
DOI:https://doi.org/10.3390/ijerph16030513
ISSN:1660-4601
ISSN:1661-7827
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/30759770
Parent Title (English):International journal of environmental research and public health
Publisher:MDPI AG
Place of publication:Basel
Document Type:Article
Language:English
Year of Completion:2019
Date of first Publication:2019/02/12
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/02/19
Tag:(surface) partial differential equations; 3D spatiotemporal resolved mathematical models; Finite Volumes; computational virology; hepatitis C virus (HCV); massively parallel multigrid solvers; mathematical models of viral RNA cycle; population dynamics; realistic geometries; viral dynamics; within-host viral modeling
Volume:16
Issue:3, Art. 513
Page Number:53
First Page:1
Last Page:53
Note:
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).
HeBIS-PPN:44625990X
Institutes:Informatik und Mathematik / Informatik
Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Open-Access-Publikationsfonds:Informatik und Mathematik
Licence (German):License LogoCreative Commons - Namensnennung 4.0