ISG15 and infection: We infected previously characterized A549 RIG-I knockout (ΔRIG-I) and non-targeted (NT) control cells [34] with either a recombinant WT (WT-R) or an E3L deletion mutant of VACV (VACV ΔE3L) and quantified viral titers and mRNA levels of ISG15 and IFN-β at 8 and 16 hours post infection (hpi).