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

Size matters: Mathematical modelling of the type‐1 interferon induction
Diana Clausznitzer, Lars Kaderali

Last modified: 2014-06-09


Retinoic acid‐inducible gene I (RIG‐I) is a cytoplasmic innate immune receptor for viral RNA. RIG‐I detects
viral RNA and triggers an antiviral response by activating the type I interferon (IFN) pathway.
While it is known that a 5′‐triphosphate end, as well as double‐strandedness of RNA constitute molecular
patterns recognised by RIG‐I, the underlying mechanism is less well established. Recent experiments show a RNA
length‐dependent activation of the IFN response, with long dsRNA evoking a larger immune response than short
RNA at non‐saturating concentrations. We developed a mathematical model of viral RNA recognition by RIG‐I, as
well as the activation of downstream players in the pathway. Our model is able to explain quantitative activation
curves of RIG‐I enzymatic activity, as well as the cellular response of IFN transcription depending on RNA length
and concentration.
Furthermore, it is consistent with additional data from structural microscopy and size exclusion experiments.
Our model predicts an important role of cooperative binding in RNA recongnition, showing how RIG‐I has
evolved to sensitively detect cellular infections by RNA viruses such as influenza. The cooperative binding of RIGI
along the length of RNA molecules ensures a large immune response even at low copy numbers of viral RNA