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HSV1 VP1-2 deubiqui...
HSV1 VP1-2 deubiquitinates STING to block type I interferon expression and promote brain infection
- Article/chapterEnglish2020
Publisher, publication year, extent ...
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2020-05-08
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Rockefeller University Press,2020
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LIBRIS-ID:oai:gup.ub.gu.se/296128
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https://gup.ub.gu.se/publication/296128URI
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https://doi.org/10.1084/jem.20191422DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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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 ΔDUB 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. © 2020 Bodda et al.
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Reinert, L. S.
(author)
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Fruhwürth, Stefanie,1987Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xfruws
(author)
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Richardo, T.
(author)
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Sun, C.
(author)
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Zhang, B. C.
(author)
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Kalamvoki, M.
(author)
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Pohlmann, A.
(author)
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Mogensen, T. H.
(author)
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Bergström, PetraGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xbpeta
(author)
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Agholme, LottaGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xaghlo
(author)
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O'Hare, P.
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Sodeik, B.
(author)
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Gyrd-Hansen, M.
(author)
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Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xzethe
(author)
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Paludan, Sören R,1972Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xriiso
(author)
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Göteborgs universitetInstitutionen för medicin, avdelningen för reumatologi och inflammationsforskning
(creator_code:org_t)
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In:The Journal of experimental medicine: Rockefeller University Press217:71540-95380022-1007
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Bodda, C.
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Reinert, L. S.
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Fruhwürth, Stefa ...
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Richardo, T.
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Sun, C.
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Zhang, B. C.
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Kalamvoki, M.
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Pohlmann, A.
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Mogensen, T. H.
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Bergström, Petra
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Agholme, Lotta
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O'Hare, P.
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Sodeik, B.
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Gyrd-Hansen, M.
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Zetterberg, Henr ...
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Paludan, Sören R ...
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