RIG-I-like helicases (RLHs) the retinoic acid inducible gene-I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) are RNA helicases that recognize viral RNA present within the cytoplasm. Functionally RIG-I and MDA5 positively regulate the IFN genes in a similar fashion, however they differ in their response to different viral species. RIG-I is essential for detecting influenza virus, Sendai virus, VSV and Japanese encephalitis virus (JEV), whereas MDA5 is essential in sensing encephalomyocarditis virus (EMCV), Mengo virus and Theiler's virus, all of which belong to the picornavirus family. RIG-I and MDA5 signalling results in the activation of IKK epsilon and (TKK binding kinase 1) TBK1, two serine/threonine kinases that phosphorylate interferon regulatory factor 3 and 7 (IRF3 and IRF7). Upon phosphorylation, IRF3 and IRF7 translocate to the nucleus and subsequently induce interferon alpha (IFNA) and interferon beta (IFNB) gene transcription.