Evaluation of the Function of the Granzyme-Mediated Antiviral System through a Mathematical Model

ABSTRACT Granzymes (gzms), the major components of cytolytic lymphocyte granules, are predominantly associated with immune regulatory processes against primary viral infections in vertebrates. By releasing into the infected cell cytosol, they initiate a rapid apoptotic process to eliminate infected cells. However, the kinetics and control mechanisms of gzms in antiviral processes have not yet been fully described. Based on earlier experimental data of ectromelia virus infection, we developed a mathematical model to evaluate the function of the gzm-mediated antiviral system. The results of simulation runs for the infections corresponded well to the experimental data, suggesting that the computational methods could be applied in researching such field. Furthermore, by altering the parameters of the model and stability analysis, we found that for viruses with various virulence, gzm-mediated defense systems cannot completely suppress the first infections in most cases, unless the virulence is limited in a narrow range. Depending on the differences of viral virulence, gzms cause oscillations of viral level in different patterns. By adding secondary immune response to the model, we found that the oscillation evoked by the gzm-mediated antiviral system has crucial significance. Consequently, we bring forward a hypothesis that most of these oscillations may allow ancillary immune responses to effectively suppress a virus as it oscillates through a minimum level.