Upon viral infection, the cytosolic receptor RIG-I and related RNA helicases, MDA5 and LGP2 recognize viral RNA and trigger intracellular signaling events that induce innate immunity, the first line of defense against microbial infection. These sentry proteins initiate a signaling cascade by interacting with the downstream partner MAVS, located to the mitochondria. Downstream signaling, resulting in the production of cytokines and interferons, has been linked to a number of pathways that ultimately activate transcription factors IRF3, IRF7 and NF-kappa-B.
Many viral antagonists of the signaling cascade leading to interferon production have been identified. The influenza A virus NS1 protein has been shown to inhibit RIG-I through direct interaction, while paramyxovirus V protein binds and inhibits MDA5 to abrogate its signaling actions. Hepatitis viruses A, B and C affect the cascade by impairing the mitochondrial MAVS protein. Downstream, cellular IRF3 and IRF7 are targeted by many viruses including Epstein-Barr virus, Ebolaviruses, Rotaviruses or Papillomaviruses.