HSV1 VP1-2 deubiquitinates STING to block type I interferon expression and promote brain infection

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HSV1 VP1-2 deubiquitinates STING to block type I interferon expression and promote brain infection. / Bodda, Chiranjeevi; Reinert, Line S.; Fruhwürth, Stefanie; Richardo, Timmy; Sun, Chenglong; Zhang, Bao Cun; Kalamvoki, Maria; Pohlmann, Anja; Mogensen, Trine H.; Bergström, Petra; Agholme, Lotta; O'Hare, Peter; Sodeik, Beate; Gyrd-Hansen, Mads; Zetterberg, Henrik; Paludan, Søren R.

In: Journal of Experimental Medicine, Vol. 217, No. 7, e20191422, 07.2020.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Bodda, C, Reinert, LS, Fruhwürth, S, Richardo, T, Sun, C, Zhang, BC, Kalamvoki, M, Pohlmann, A, Mogensen, TH, Bergström, P, Agholme, L, O'Hare, P, Sodeik, B, Gyrd-Hansen, M, Zetterberg, H & Paludan, SR 2020, 'HSV1 VP1-2 deubiquitinates STING to block type I interferon expression and promote brain infection', Journal of Experimental Medicine, vol. 217, no. 7, e20191422. https://doi.org/10.1084/jem.20191422

APA

Bodda, C., Reinert, L. S., Fruhwürth, S., Richardo, T., Sun, C., Zhang, B. C., Kalamvoki, M., Pohlmann, A., Mogensen, T. H., Bergström, P., Agholme, L., O'Hare, P., Sodeik, B., Gyrd-Hansen, M., Zetterberg, H., & Paludan, S. R. (2020). HSV1 VP1-2 deubiquitinates STING to block type I interferon expression and promote brain infection. Journal of Experimental Medicine, 217(7), [ e20191422]. https://doi.org/10.1084/jem.20191422

CBE

Bodda C, Reinert LS, Fruhwürth S, Richardo T, Sun C, Zhang BC, Kalamvoki M, Pohlmann A, Mogensen TH, Bergström P, Agholme L, O'Hare P, Sodeik B, Gyrd-Hansen M, Zetterberg H, Paludan SR. 2020. HSV1 VP1-2 deubiquitinates STING to block type I interferon expression and promote brain infection. Journal of Experimental Medicine. 217(7):Article e20191422. https://doi.org/10.1084/jem.20191422

MLA

Vancouver

Author

Bodda, Chiranjeevi ; Reinert, Line S. ; Fruhwürth, Stefanie ; Richardo, Timmy ; Sun, Chenglong ; Zhang, Bao Cun ; Kalamvoki, Maria ; Pohlmann, Anja ; Mogensen, Trine H. ; Bergström, Petra ; Agholme, Lotta ; O'Hare, Peter ; Sodeik, Beate ; Gyrd-Hansen, Mads ; Zetterberg, Henrik ; Paludan, Søren R. / HSV1 VP1-2 deubiquitinates STING to block type I interferon expression and promote brain infection. In: Journal of Experimental Medicine. 2020 ; Vol. 217, No. 7.

Bibtex

@article{81e1d408c5ac44deae2ca4a59fcc3cb7,
title = "HSV1 VP1-2 deubiquitinates STING to block type I interferon expression and promote brain infection",
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 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.",
author = "Chiranjeevi Bodda and Reinert, {Line S.} and Stefanie Fruhw{\"u}rth and Timmy Richardo and Chenglong Sun and Zhang, {Bao Cun} and Maria Kalamvoki and Anja Pohlmann and Mogensen, {Trine H.} and Petra Bergstr{\"o}m and Lotta Agholme and Peter O'Hare and Beate Sodeik and Mads Gyrd-Hansen and Henrik Zetterberg and Paludan, {S{\o}ren R.}",
year = "2020",
month = jul,
doi = "10.1084/jem.20191422",
language = "English",
volume = "217",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "7",

}

RIS

TY - JOUR

T1 - HSV1 VP1-2 deubiquitinates STING to block type I interferon expression and promote brain infection

AU - Bodda, Chiranjeevi

AU - Reinert, Line S.

AU - Fruhwürth, Stefanie

AU - Richardo, Timmy

AU - Sun, Chenglong

AU - Zhang, Bao Cun

AU - Kalamvoki, Maria

AU - Pohlmann, Anja

AU - Mogensen, Trine H.

AU - Bergström, Petra

AU - Agholme, Lotta

AU - O'Hare, Peter

AU - Sodeik, Beate

AU - Gyrd-Hansen, Mads

AU - Zetterberg, Henrik

AU - Paludan, Søren R.

PY - 2020/7

Y1 - 2020/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85084404032&partnerID=8YFLogxK

U2 - 10.1084/jem.20191422

DO - 10.1084/jem.20191422

M3 - Journal article

C2 - 32383759

AN - SCOPUS:85084404032

VL - 217

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 7

M1 - e20191422

ER -