Mathematical Modeling of Signaling Pathways Leading to Type I IFN Gene Expression

Many viruses can escape cellular innate antiviral immune responses by encoding one or more proteins to inhibit the induction of type I interferons (IFN-alpha/beta), which leads to the occurrence of major diseases. However, the mechanisms how some virus-encoded proteins inhibit IFN-alpha/beta induction have not yet been fully understood. Based on available literature and experimental data of classical swine fever virus (CSFV), in this study, we develop a mathematical model of virus- and dsRNA-triggered type I IFN signaling pathways, and investigate the quantitative relationship between the dose of the transfected plasmid and the inhibitory effects of N-pro or E-rns. Our simulation results showed that CSFV N-pro inhibited both dsRNA- and virus- induced IFN-beta expression, and E-rns only inhibited exogenous dsRNAtriggered IFN-beta production, which are agreement with experimental data. The dose-dependent inhibition by N-pro or E-rns was observed when the transfected plasmid was less than 1.5 mu g. Furthermore, when the plasmid was more than 1.5 mu g, the inhibitory effects of both N-pro and E-rns can reach maximum. These results provide insight into systems properties and generation of hypotheses for further research.