Mathematical modelling of OAS2 activation by dsRNA and effects of dsRNA lengths

Abstract

The activation of 2'-5'-oligoadenylate synthetase (OAS) enzymes by direct interaction with viral double-stranded RNA (dsRNA) is a key part of the innate immune response to viral infection. A downstream effect of the OAS-dsRNA interaction is to degrade the single-stranded RNA to prevent the spread of the virus. The activation of OAS2, one of the members of the OAS family, depends on dsRNA length. Combining in vitro experiments and mathematical modelling, we test different hypotheses for the OAS2 activation mechanisms by its cofactor dsRNA. After model calibration and selection, the cooperative binding of multiple OAS2 to a single dsRNA is shown to best represent the effect of its cofactor length on enzyme activity.

Keywords

• oas2
• dsrna
• lengths
• concentrations
• enzyme activation
• mathematical modelling
• enzymatic activity