3D spatially resolved HCV replication models simulated at realistic cell geometries

The Hepatitis C virus steadily jeopardizes the health of the host during chronic infection.

The HCV viral RNA replication cycle is a dynamic process occurring in three dimensional space (3D). HCV-generated replication factories are housed within virus-induced intracellular structures termed membranous webs (MW) which are derived from the Endoplasmatic Reticulum (ER).

We present 3D spatio-temporal resolved diffusion-reaction models of the HCV RNA replication cycle by means of partial differential equation (PDE) descriptions. We present models of different complexity evaluated each upon realistic reconstructed intracellular compartments (ER/MW).

While the most simple model describes the dynamics of the basic components of the HCV RNA replication cycle, namely HCV RNA, non-structural viral proteins (NSPs) and a host factor, extended models are based upon two additional parameters: Different aggregate states of HCV RNA and NSPs, and population dynamics inspired diffusion and reaction coefficients instead of multilinear ones. The combination of both aspects enables realistic modeling of viral replication at all scales.

In particular, the replication complex state we introduce consists of HCV RNA together with a defined amount of NSPs. Indeed, the combination of spatial resolution and different aggregate states allows to mimic a cis requirement for HCV RNA replication. While in part our model still uses heuristic parameters, our simulations allow fitting core aspects of virus reproduction at least qualitatively. Our spatio-temporal resolved ansatz paves new ways for understanding intricate spatial-defined processes central to specific aspects of virus life cycles.

Publication History

Article published online:
26 January 2022