Kok2020 - IFNalpha-induced signaling in Huh7.5 cells

The proposed ODE model describes dynamics of IFNalpha-induced signaling in Huh7.5 cells for a time scale up to 32 hours after stimulation with IFNalpha. The model consists of an IFN receptor model, formation/degradation and cytoplasmic/nuclear shuttling of STAT1-homodimers, STAT1-STAT2-heterodimers and STAT1-STAT2-IRF9 (ISGF3) complexes. On top, formation of feedback proteins STAT1, STAT2, IRF9, USP18, SOCS1, SOCS3 and IRF2 and corresponding influences on IFNalpha signaling dynamics was incorporated. The model was calibrated by dose response and time course measurements over 32 hours as well as time courses for USP18 inhibition and overexpression experiments. As a special focus, the model is able to describe dose-dependent sensitization and desensitization of IFNalpha signaling in form of double treatment experiments at 0h and 24h.