Quantitative Analysis of Hepatitis C NS5A Viral Protein Dynamics on the ER Surface.

Viruses
Markus M KnodelGabriel Wittum

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...Continue Reading

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Citations

Jun 6, 2018·Viruses·John M Murray, Ruy M Ribeiro
Feb 15, 2019·International Journal of Environmental Research and Public Health·Markus M KnodelGabriel Wittum

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Methods Mentioned

BETA
fluorescence recovery after photobleaching
confocal microscopic microscopy

Software Mentioned

NeuRA2
R

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