MDA5, ISG15, and ISG56 have been reported that can be upregulated by HCMV infection [15,20], while the HCMV immediate early gene 1 (IE1) can activate STAT1 by re-routing IL-6 signaling [21]..The above results indicated that at the early stage post HCMV infection, both HCMV strains activated the expression of ISGs, while in cells infected with Han, which can express pUL138, a more significant increase in ISG production was observed. This evidence concerns the gene ISG15 and cytomegalovirus infection.