Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface
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 dynamic...
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MDPI AG
2018-01-01
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| Series: | Viruses |
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| Online Access: | http://www.mdpi.com/1999-4915/10/1/28 |
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| author | Markus M. Knodel Arne Nägel Sebastian Reiter Andreas Vogel Paul Targett-Adams John McLauchlan Eva Herrmann Gabriel Wittum |
| author_facet | Markus M. Knodel Arne Nägel Sebastian Reiter Andreas Vogel Paul Targett-Adams John McLauchlan Eva Herrmann Gabriel Wittum |
| author_sort | Markus M. Knodel |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T21:42:40Z |
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| id | doaj.art-f7cd709d58a5428d8b7438cddcc2ec8a |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-14T21:42:40Z |
| publishDate | 2018-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-f7cd709d58a5428d8b7438cddcc2ec8a2022-12-21T22:46:26ZengMDPI AGViruses1999-49152018-01-011012810.3390/v10010028v10010028Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER SurfaceMarkus M. Knodel0Arne Nägel1Sebastian Reiter2Andreas Vogel3Paul Targett-Adams4John McLauchlan5Eva Herrmann6Gabriel Wittum7Goethe Center for Scientific Computing (G-CSC), Goethe Universität Frankfurt, Kettenhofweg 139, 60325 Frankfurt am Main, GermanyGoethe Center for Scientific Computing (G-CSC), Goethe Universität Frankfurt, Kettenhofweg 139, 60325 Frankfurt am Main, GermanyGoethe Center for Scientific Computing (G-CSC), Goethe Universität Frankfurt, Kettenhofweg 139, 60325 Frankfurt am Main, GermanyGoethe Center for Scientific Computing (G-CSC), Goethe Universität Frankfurt, Kettenhofweg 139, 60325 Frankfurt am Main, GermanyMedivir AB, Department of Biology, Huddinge 141 22, SwedenMRC-University of Glasgow Centre for Virus Research, 464 Bearsden Road, Glasgow G61 1QH, UKDepartment of Medicine, Institute for Biostatistics and Mathematic Modeling, Goethe Universität Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyGoethe Center for Scientific Computing (G-CSC), Goethe Universität Frankfurt, Kettenhofweg 139, 60325 Frankfurt am Main, GermanyExploring 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.http://www.mdpi.com/1999-4915/10/1/28computational virologyhepatitis C virus (HCV)viral dynamicswithin-host viral modellingparameter estimation3D spatio-temporal resolved mathematical modelsrealistic geometries(surface) partial differential equationsFinite Volumesmassively parallel multigrid solvers |
| spellingShingle | Markus M. Knodel Arne Nägel Sebastian Reiter Andreas Vogel Paul Targett-Adams John McLauchlan Eva Herrmann Gabriel Wittum Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface Viruses computational virology hepatitis C virus (HCV) viral dynamics within-host viral modelling parameter estimation 3D spatio-temporal resolved mathematical models realistic geometries (surface) partial differential equations Finite Volumes massively parallel multigrid solvers |
| title | Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface |
| title_full | Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface |
| title_fullStr | Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface |
| title_full_unstemmed | Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface |
| title_short | Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface |
| title_sort | quantitative analysis of hepatitis c ns5a viral protein dynamics on the er surface |
| topic | computational virology hepatitis C virus (HCV) viral dynamics within-host viral modelling parameter estimation 3D spatio-temporal resolved mathematical models realistic geometries (surface) partial differential equations Finite Volumes massively parallel multigrid solvers |
| url | http://www.mdpi.com/1999-4915/10/1/28 |
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