The first indication of potential involvement of the cytoplasmic RNA helicases in sensing DNA virus infection came from the knockdown of MAVS (also called IPS-1), the sole known adaptor for RIG-I and MDA5 signaling, in which IFN-β induction was shown to be substantially reduced in MAVS-deficient mouse embryo fibroblasts following the infection by modified vaccinia Ankara [46]. The gene discussed is IFIH1; the disease is infection.