Recently, professor Gao Chengjiang's team made new progress in the field of natural immune regulation. And published the paper titled “USP18 positively regulates innate antiviral immunity by promoting K63-linked polyubiquitination of MAVS” in the international academic journal Nature Communications (IF=13.611). Professor Gao Chengjiang is the corresponding author, and young teacher Zheng Yi is the co-corresponding author, and Doctoral candidate Hou Jinxiu is the first author unit and the only corresponding author.
The previous study published by Professor Gao Chengjiang’s team in Nature Immunology (2017, 18:214-224) showed that viral infection stimulates the enrichment of E3 ubiquitin ligase TRIM31 to mitochondria, which directly promotes the ubiquitination of K63 of MAVS and the aggregation of MAVS, thus activating the downstream antiviral type I interferon signaling pathway.TRIM31 is the only E3 ubiquitin ligase that has been found to specifically regulate the ubiquitination of MVAS K63, but the mechanism of how TRIM31 locates mitochondria remains unclear.
By screening the mitochondrial deubiquitination enzymes, it was found that the deubiquitination enzyme USP18 specifically enhanced the ubiquitination modification level of MAVS. Further studies showed that RNA virus stimulation caused USP18 to be enriched to mitochondria, specifically interacting with MAVS, promoting the ubiquitination modification and aggregation of MAVS at K63, and then up-regulating the expression and secretion of type I interferon. In line with this, mice with USP18 deletions were more susceptible to RNA viruses. Mechanism studies have shown that USP18, as a connector molecule, promotes the translocation of TRIM31 to mitochondria and enhances the binding of TRIM31 to MAVS to promote its activation by its function independent of its enzyme activity. This study revealed that USP18 is an important regulatory molecule of TRIM31 translocation to mitochondria, which once again proved that TRIM31 is an important molecule in the activation of host natural immunity by RNA virus infection, requiring fine multi-level regulation.
Paper link: https://www.nature.com/articles/s41467-021-23219-4
