Dynamics and Sensitivity of the Lifecycle of Hepatitis B Virus

A detailed mathematical model has been developed for the dynamics of hepatitis B virus (HBV) infection in a single cell. It provides a platform for a better quantitative understanding of the biochemical kinetics of the HBV lifecycle. The model is used to study the sensitivity of virus growth, providing a clear ranking of intracellular virus replication processes with respect to their contribution to net viral production. The stochastic formulation of the model enables the quantification of the variability characteristics in viral production, the probability of productive infection and the secretion of protein- and genome-deficient viral particles. An essential difference in infection efficiency between deterministic and stochastic models has been revealed. For example, in the case of MOI=1, the mean value of the total number of mature virions released during the lifecycle of the infection in the stochastic model is 1.06, whereas, in the deterministic model, its value is less than one thousandth and thus close to 0. The model is also used to quantitatively predict the effect of combinations of direct-acting antivirals, such as small interfering RNAs, capsid inhibitors and nucleoside analogues. The model shows that the inhibitory effect of siRNA on viral production is approximately two orders of magnitude higher than that of nucleoside analogues and capsid inhibitors.