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

Markus M. Knodel*, Arne Nägel, Sebastian Reiter, Andreas Vogel, Paul Targett-Adams, John McLauchlan, Eva Herrmann, Gabriel Wittum

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish (US)
Article number28
JournalViruses
Volume10
Issue number1
DOIs
StatePublished - Jan 8 2018

Keywords

  • (Surface) partial differential equations
  • 3D spatio-temporal resolved mathematical models
  • Computational virology
  • Finite volumes
  • Hepatitis C virus (HCV)
  • Massively parallel multigrid solvers
  • Parameter estimation
  • Realistic geometries
  • Viral dynamics
  • Within-host viral modelling

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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