Ribonuclease L (RNase L) is an ankyrin (ANK) repeat domain containing dual endoribonuclease-pseudokinase which is encoded by RNASEL gene (Wreschner DH et al. 1982; Zhou A et al.1993; Hassel BA et al. 1993; Huang H et al. 2014; Han Y et al. 2014). Activated RNase L forms a homodimer (Dong B & Silverman RH 1995) which cleaves within single-stranded regions of different RNA substrates, predominantly after UpAp and UpUp dinucleotides, leaving 2',3'-cyclic phosphoryl and 5'-hydroxyl groups at the termini of the RNA cleavage products (Wreschner DH et al. 1981; Floyd-Smith G et al. 1981; Han Y et al. 2012; Cooper DA et al. 2014). The antiviral function of RNase L extends beyond direct cleavage of viral RNA and includes also cleavage of cellular RNA such as mRNA and rRNA that is required for viral replication (Wreschner DH et al. 1981; Silverman RH et al.1983; Brennan-Laun SE et al. 2014; Cooper DA et al. 2014). RNase L induces apoptosis to eliminate virus-infected cells and autophagy to limit viral infections in some circumstances (Zhou A et al. 1997; Castelli JC et al. 1997; Chakrabarti A et al. 2012). Depending on the cell type and basal levels of RNase L, viral and cellular RNA cleavage products induce signaling to the IFN beta gene through RIG-I and/or MDA5 and MAVS (Malathi K et al. 2007; Banerjee S etl al. 2014).