ISG15 and viral infectious disease: Both IFIT1 and ISG15 are pro-inflammatory genes and are associated with viral resistance and defense in human.[63–65]ISG15 is IFN-inducible, and the expression of ISG15 prevents IFN amplification and auto-inflammation in turn.[66]ISG15-deficient patients with viral diseases had a high level of IFN-α/β,[66] while decreased IFIT1 expression was correlated with the increased HBV replication.[65] The downregulation of IFN-induced proteins, including IFIT1, IFIT2, IFIT3, IFIT5, ISG15, and IFI6, might suggest the downregulation of IFN production.