ISG15 is one of scores of ISGs which may be induced directly or indirectly by virus proteins or byproducts of virus infection [43]; however, as expression of ISG15 mRNA and protein was similar between ΔNS1/2 and WT virus infection of MLE-15 cells, it is unlikely NS1/NS2 has a role in modifying ISG15. Here, ISG15 is linked to viral infectious disease.