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 > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| 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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