TY  - JOUR
A1  - Knodel, Markus Michael
A1  - Nägel, Arne
A1  - Reiter, Sebastian
A1  - Vogel, Andreas
A1  - Targett-Adams, Paul
A1  - McLauchlan, John
A1  - Herrmann, Eva
A1  - Wittum, Gabriel
T1  - Quantitative analysis of hepatitis C NS5A viral protein dynamics on the ER surface
T2  - Viruses
N2  - 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.
KW  - computational virology
KW  - hepatitis C virus (HCV)
KW  - viral dynamics
KW  - within-host viral modelling
KW  - parameter estimation
KW  - 3D spatio-temporal resolved mathematical models
KW  - realistic geometries
KW  - (surface) partial differential equations
KW  - Finite Volumes
KW  - massively parallel multigrid solvers
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45739
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-457390
SN  - 1999-4915
N1  - © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
VL  - 10
IS  - 1, Art. 28
SP  - 1
EP  - 26
PB  - MDPI
CY  - Basel
ER  -