ISG15 and viral infectious disease: IFI6 is an IFN-stimulated gene (ISG) whose expression is highly regulated by the stimulation of IFN-I-alpha, which restricts various kinds of virus infections by targeting different stages of the viral life cycle [12], while ISG15 is upregulated in response to type I and type III IFN and leads to the conjugation of lysine residues of target proteins, a process termed ISGylation, with widely recognized antiviral activity [13].