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However, the regulation of the NF90-SG pathway remains largely unclear. We found that Tim-3, an immune checkpoint inhibitor, promotes the ubiquitination and degradation of NF90 and inhibits NF90-SG-mediated antiviral immunity. Vesicular stomatitis virus (VSV) infection induces the up-regulation and activation of Tim-3 in macrophages, which in turn recruit the E3 ubiquitin ligase TRIM47 to the zinc finger domain of NF90 and initiate a proteasome-dependent degradation via K48-linked ubiquitination at Lys297. Targeted inactivation of Tim-3 enhances the NF90 downstream SG formation by selectively increasing the phosphorylation of protein kinase R and eukaryotic translation initiation factor 2\u03b1, the expression of SG markers G3BP1 and TIA-1, and protecting mice from VSV challenge. These findings provide insights into the crosstalk between Tim-3 and other receptors in antiviral innate immunity and its related clinical significance.<\/jats:p>","DOI":"10.7554\/elife.66501","type":"journal-article","created":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T08:00:35Z","timestamp":1623312035000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.66501","source":"Crossref","is-referenced-by-count":24,"title":["Ubiquitination and degradation of NF90 by Tim-3 inhibits antiviral innate immunity"],"prefix":"10.7554","volume":"10","author":[{"given":"Shuaijie","family":"Dou","sequence":"first","affiliation":[{"name":"Beijing Institute of Basic Medical Sciences, Beijing, China"},{"name":"Anhui Medical University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxian","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Institute of Basic Medical Sciences, Beijing, China"},{"name":"Institute of Immunology, Medical School of 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