HCMV infection triggers expression of ISG, which the virus counters by impairing the IFN signaling pathway, degrading the double-stranded RNA sensor RIG-I (Retinoic acid-inducible gene I) and “repurposing” ISGs such as Tetherin to enhance rather than restrict viral replication (reviewed in Amsler et al., 2013). The gene discussed is RIGI; the disease is cytomegalovirus infection.