Regulation of signaling mediated by nucleic acid sensors for innate interferon-mediated responses during viral infection

Takaoka, Akinori; Yamada, Taisho

Type I and type III interferons are important anti-viral cytokines that are massively induced during viral infection. This dynamic process is regulated by many executors and regulators for efficient eradication of invading viruses and protection from harmful, excessive responses. An array of innate sensors recognizes virus-derived nucleic acids to activate their downstream signaling to evoke cytokine responses including interferons. In particular, a cytoplasmic RNA sensor RIG-I (retinoic acid-inducible gene I) is involved in the detection of multiple types of not only RNA viruses but also DNA viruses. Accumulating findings have revealed that activation of nucleic acid sensors and the related signaling mediators is regulated on the basis of post-translational modification such as ubiquitination, phosphorylation and ADP-ribosylation. In addition, long non-coding RNAs (lncRNAs) have been implicated as a new class of regulators in innate signaling. A comprehensive understanding of the regulatory mechanisms of innate sensor activation and its signaling in host–virus interaction will provide a better therapeutic strategy to efficiently control viral infection and maintain immune homeostasis.