@article{discovery10098429,
            note = {This article is distributed under the terms of an Attribution-Noncommercial-Share Alike-No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution-Noncommercial-Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/)},
           title = {HSV1 VP1-2 deubiquitinates STING to block type I interferon expression and promote brain infection},
          number = {7},
         journal = {Journal of Experimental Medicine},
           month = {July},
          volume = {217},
            year = {2020},
          author = {Bodda, C and Reinert, LS and Fruhw{\"u}rth, S and Richardo, T and Sun, C and Zhang, B-C and Kalamvoki, M and Pohlmann, A and Mogensen, TH and Bergstr{\"o}m, P and Agholme, L and O'Hare, P and Sodeik, B and Gyrd-Hansen, M and Zetterberg, H and Paludan, SR},
             url = {https://doi.org/10.1084/jem.20191422},
        abstract = {Herpes simplex virus (HSV) is the main cause of viral encephalitis in the Western world, and the type I interferon (IFN) system is important for antiviral control in the brain. Here, we have compared Ifnb induction in mixed murine brain cell cultures by a panel of HSV1 mutants, each devoid of one mechanism to counteract the IFN-stimulating cGAS-STING pathway. We found that a mutant lacking the deubiquitinase (DUB) activity of the VP1-2 protein induced particularly strong expression of Ifnb and IFN-stimulated genes. HSV1 {\ensuremath{\Delta}}DUB also induced elevated IFN expression in murine and human microglia and exhibited reduced viral replication in the brain. This was associated with increased ubiquitination of STING and elevated phosphorylation of STING, TBK1, and IRF3. VP1-2 associated directly with STING, leading to its deubiquitination. Recruitment of VP1-2 to STING was dependent on K150 of STING, which was ubiquitinated by TRIM32. Thus, the DUB activity of HSV1 VP1-2 is a major viral immune-evasion mechanism in the brain.}
}