The importance of ISG15 in defeating viral infections is underlined by the fact that several viruses counteract ISGylation and express proteins that either bind ISG15 (Influenza B) [29,30] or proteases that deconjugate ISG15 from proteins (foot-and-mouth disease virus [31], Crimean Congo Hemorrhagic Fever Virus [32,33], SARS-corona virus [34], MERS-corona virus [34]). Here, ISG15 is linked to viral infectious disease.