Moreover, whereas ubiquitin, Nedd8, and SUMO are constitutively expressed in cells, ISG15 is strongly induced by type I interferons (IFN-α and IFN-β) [23] in response to infections (viral, bacterial, and parasite) [24,25], polyinosinic:polycytidylic acid (poly I:C) [26], or lipopolysaccharide [27]. Here, ISG15 is linked to infection.