Advanced Hepatitis C Virus Replication PDE Models within a Realistic Intracellular Geometric Environment

Knodel M, Targett-Adams P, Grillo A, Herrmann E, Wittum G (2019)

Publication Type: Journal article

Publication year: 2019

Journal

International Journal of Environmental Research and Public Health MDPI

Book Volume: 16

Journal Issue: 3

DOI: 10.3390/ijerph16030513

Abstract

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.

Authors with CRIS profile

Markus Knodel Lehrstuhl für Angewandte Mathematik (Modellierung und Numerik)

Involved external institutions

Goethe-Universität Frankfurt am Main DE Germany (DE) Medivir AB SE Sweden (SE) Politecnico di Torino IT Italy (IT)

How to cite

APA:

Knodel, M., Targett-Adams, P., Grillo, A., Herrmann, E., & Wittum, G. (2019). Advanced Hepatitis C Virus Replication PDE Models within a Realistic Intracellular Geometric Environment. International Journal of Environmental Research and Public Health, 16(3). https://dx.doi.org/10.3390/ijerph16030513

MLA:

Knodel, Markus, et al. "Advanced Hepatitis C Virus Replication PDE Models within a Realistic Intracellular Geometric Environment." International Journal of Environmental Research and Public Health 16.3 (2019).

BibTeX: Download