ANTI-VIRAL TETRIS: Modulation of the Innate Anti-Viral Immune Response by A20

摘要

The A20 protein has emerged as an important negative regulator of Toll like receptor (TLR) andretinoic acid-inducible gene 1 (RIG-I)-mediated anti-viral signaling. A20 functions both as aRING-type E3 ubiquitin ligase and as a de-ubiquitinating enzyme. Nuclear factor kappa B (NF-kB) and interferon regulatory factor (IRF) pathways are targeted by A20 through mechanisms that appear to be both overlapping and distinct, resulting in the downregulation of interferon alpha/beta (IFNa/beta) production. This review specifically details the impact of A20 on the cytosolic RIG-I/MDA5 pathway, a process that is less understood than that of NF-kB but is essential for the regulation of the innate immune response to viral infection.