Quantitative analysis of hepatitis C NS5A viral protein dynamics on the ER surface

Knodel, M. M., Nägel, A., Reiter, S., Vogel, A., Targett-Adams, P., McLauchlan, J. , Herrmann, E. and Wittum, G. (2018) Quantitative analysis of hepatitis C NS5A viral protein dynamics on the ER surface. Viruses, 10(1), 28. (doi:10.3390/v10010028) (PMID:29316722)

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Abstract

Exploring biophysical properties of virus-encoded components and their requirement for virus replication is an exciting new area of interdisciplinary virological research. To date, spatial resolution has only rarely been analyzed in computational/biophysical descriptions of virus replication dynamics. However, it is widely acknowledged that intracellular spatial dependence is a crucial component of virus life cycles. The hepatitis C virus-encoded NS5A protein is an endoplasmatic reticulum (ER)-anchored viral protein and an essential component of the virus replication machinery. Therefore, we simulate NS5A dynamics on realistic reconstructed, curved ER surfaces by means of surface partial differential equations (sPDE) upon unstructured grids. We match the in silico NS5A diffusion constant such that the NS5A sPDE simulation data reproduce experimental NS5A fluorescence recovery after photobleaching (FRAP) time series data. This parameter estimation yields the NS5A diffusion constant. Such parameters are needed for spatial models of HCV dynamics, which we are developing in parallel but remain qualitative at this stage. Thus, our present study likely provides the first quantitative biophysical description of the movement of a viral component. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specfic aspects of virus life cycles.

Item Type:Articles
Keywords:(Surface) partial differential equations, 3D spatio-temporal resolved mathematical models, Finite Volumes, computational virology, hepatitis C virus (HCV), massively parallel multigrid solvers, parameter estimation, realistic geometries, viral dynamics, within-host viral modelling.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McLauchlan, Professor John
Authors: Knodel, M. M., Nägel, A., Reiter, S., Vogel, A., Targett-Adams, P., McLauchlan, J., Herrmann, E., and Wittum, G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Viruses
Publisher:MDPI
ISSN:1999-4915
ISSN (Online):1999-4915
Published Online:08 January 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Viruses 10(1): 28
Publisher Policy:Reproduced under a Creative Commons License

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