Anti-viral tetris: Modulation of the innate anti-viral immune response by a20

Abstract

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 a RING-type E3 ubiquitin ligase and as a de-ubiquitinating enzyme. Nuclear factor kappa B (NF-KB) and interferon regulatory factor (TRF) pathways are targeted by A20 through mechanisms that appear to be both overlapping and distinct, resulting in the downregulation of interferon a/j3 (IFNa/j3) production. This review specifically details the impact of A20 on the cytosolic RTG-TIMDAS pathway, a process that is less understood than that ofNF-KB but is essential for the regulation of the innate immune response to viral infection.