Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Spatial spread of hepatitis C virus in vivo and in vitro – analyzing single cell dynamics
Fredrik Graw, Harel Dahari, Ruy M. Ribeiro, Alan S. Perelson

Last modified: 2014-06-09


Intrahepatic hepatitis C virus (HCV) infection dynamics are still poorly understood, including the preferred
mode of viral propagation and the rate of turnover of infected hepatocytes during chronic infection. We
developed new mathematical methods and spatially explicit models to analyze and quantify the cellular
dynamics of HCV infection based on data from liver biopsy material and in vitro cultures.
Our work suggests that infected cells as observed in 2D liver biopsy sections form clusters ranging in size
from 4‐50 cells. In addition, the HCV RNA content in each infected cell was measured and found to decrease
from the cell that presumably founded the cluster to cells at the cluster edge, suggesting local spread of
infection from the founder cell outward. Using a mathematical model for the intracellular replication of HCV,
which predicts the accumulation of viral RNA over time, our preliminary estimates indicate that cells in a
cluster have been infected for less than a week.
To determine and quantify the processes that have shaped the observed spatial distribution of infected cells
and the viral topography of clusters, we developed spatially explicit models of viral replication and spread.
Parameterizing our model by results from experimental data on HCV foci expansion in the presence and
absence of agents that can block various modes of viral transmission, we are able to form inferences about
infection dynamics in solid tissues from static spatial data.