The antiviral innate immunity response follows viral infection and the detection of viral components by the host pattern recognition receptors (PRRs), consisting of two main families: Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs). The Toll-like receptors are located at the cell surface and recognize extracellular viruses, whereas the RIG-I-like receptors are present in the cytoplasm and recognize 5'-phosphate-containing viral RNA. The family of RIG-I-like receptors is composed of three members: retinoic acid inducible gene-I (RIG-I), melanoma differentiation-associated gene 5 (MDA5), and laboratory of genetics and physiology 2 (LGP2). While MDA5 is essential for the recognition of dsRNA of Picornaviruses, RIG-I is involved in the recognition of uncapped 5'-phosphate dsRNA or ssRNA found in Flaviviruses, Orthomyxoviruses, Paramyxoviruses, Rhabdoviruses and the Japanese encephalitis virus. RIG-I is also implicated in the sensing of Epstein-Barr virus non-translated EBER RNAs.Following ligand recognition, RIG-I and MDA5 initiate an intracellular signaling cascade leading to the production of type-1 interferon and proinflammatory cytokines, which trigger the antiviral innate immune response. Upon ligand binding, RIG-I and MDA5 both interact with the adaptor protein IPS-1, which in turn signal through TRAF3, TANK, TBK1, and IKKε leading to the activation and dimerization of phosphorylated IRF-3 and IRF-7. These two transcription factors translocate to the nucleus and induce the transcription of type-1 interferons. IPS-1 can also interact with TRAF2, TRAF6, FADD, and RIPK1, leading to the activation of the NF-κB pathway and subsequent transcription of IFN-β. Although LPG2 is able to bind dsRNA, it lacks a downstream signal domain and therefore does not signal itself. However, LPG2 has an inhibitory function in RIG-I/MDA5-mediated signaling. Viruses have adapted strategies to interfere with the host immune response. Various proteins encoded by RNA viruses are able to antagonize the RIG-I-like receptors signaling pathway.