Although a functional p53 binding site adjacent to the core ISRE site of ISG15 has been reported, upregulation of ISG15 has been observed after dsRNA stimulation rather than in response to IFN treatment or virus infection, suggesting that the observed effects on ISG15 could be mediated through p53-dependent upregulation of TLR3 activity [109]. Here, TLR3 is linked to viral infectious disease.