Intracellular “in silico microscopes” – fully 3D spatial Hepatitis C virus replication model simulations

To face present and upcoming virus pandemics and endemics such as the Hepatitis C virus (HCV) induced liver damages, detailed quantitative biophysical understanding of intracellular virus replication mechanisms is necessary. Understanding the interplay of form and function might allow to figure out attack points for the strategic development of direct antiviral agents (DAA) and vaccines. Biophysical research of spatio-temporal evolution of virus replication so far is rare. We are developing a framework to allow for spatio-temporal resolved virus replication simulations based on advanced numerical mathematical methods. This study presents an advanced highly nonlinear model of the HCV genome replication cycle. The diffusion-reaction model describes the interplay of the major components of the viral RNA (vRNA) cycle, which are the non structural viral proteins (NSP), the vRNA, and a host factor. Technically, we couple surface PDEs (sufPDEs) on the 2D Endoplasmatic Reticulum (ER) with PDEs in the 3D cytosol. The model is evaluated at realistic reconstructed cell geometries, the geometries are based on experimental data. The simulations reproduce the effects of NSPs which are restricted to the ER surface with those appearing in the cytosol volume. The visualization of the simulation resembles a look into some sort of "in silico" microscope. The output data approach quantitative experimental data and request experimental model validation. [2]

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Article published online:
23 January 2024