Acetylation-Dependent Deubiquitinase OTUD3 Controls MAVS Activation in Innate Antiviral Immunity.

摘要: Accurate regulation of innate immunity is necessary for the host to efficiently respond invading pathogens and avoid excessive harmful immune pathology. Here we identified OTUD3 as an acetylation-dependent deubiquitinase that restricts antiviral signaling. deficiency in mice results enhanced immunity, a diminished viral load, morbidity. directly hydrolyzes lysine 63 (Lys63)-linked polyubiquitination MAVS thus shuts off response. Notably, catalytic activity relies on acetylation its Lys129 residue. In response virus infection, acetylated removed by SIRT1, which promptly inactivates allows timely induction immunity. Importantly, acetyl-OTUD3 levels are inversely correlated with IFN-β expression influenza patients. These findings establish repressor uncover previously unknown regulatory mechanism tightly controlled ensure activation defense.