HSV‐1 ICP27 targets the TBK1‐activated STING signalsome to inhibit virus‐induced type I IFN expression

Maria H Christensen, Søren B Jensen, Juho Jalmari Miettinen, Stefanie Luecke, Thaneas Prabakaran, Line S Reinert, Thomas Mettenleiter, Zhijian J Chen, David M Knipe, Rozanne M Sandri-Goldin, Lynn W Enquist, Rune Hartmann, Trine H Mogensen, Stephen A Rice, Tuula Anneli Nyman, Sampsa Matikainen, Søren R Paludan

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Herpes simplex virus (HSV) 1 stimulates type I IFN expression through the cGAS–STING–TBK1 signaling axis. Macrophages have recently been proposed to be an essential source of IFN during viral infection. However, it is not known how HSV‐1 inhibits IFN expression in this cell type. Here, we show that HSV‐1 inhibits type I IFN induction through the cGAS–STING–TBK1 pathway in human macrophages, in a manner dependent on the conserved herpesvirus protein ICP27. This viral protein was expressed de novo in macrophages with early nuclear localization followed by later translocation to the cytoplasm where ICP27 prevented activation of IRF3. ICP27 interacted with TBK1 and STING in a manner that was dependent on TBK1 activity and the RGG motif in ICP27. Thus, HSV‐1 inhibits expression of type I IFN in human macrophages through ICP27‐dependent targeting of the TBK1‐activated STING signalsome.
Original languageEnglish
JournalEMBO Journal
Volume2016
Issue number35
Pages (from-to)1385-1399
Number of pages15
ISSN0261-4189
DOIs
Publication statusPublished - 27 Jul 2016
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 1182 Biochemistry, cell and molecular biology
  • HSV-1
  • INNATE IMMUNE-RESPONSE
  • INNATE IMMUNITY
  • ICP27
  • IFN response

Cite this

Christensen, M. H., Jensen, S. B., Miettinen, J. J., Luecke, S., Prabakaran, T., Reinert, L. S., ... Paludan, S. R. (2016). HSV‐1 ICP27 targets the TBK1‐activated STING signalsome to inhibit virus‐induced type I IFN expression. EMBO Journal, 2016(35), 1385-1399. https://doi.org/10.15252/embj.201593458
Christensen, Maria H ; Jensen, Søren B ; Miettinen, Juho Jalmari ; Luecke, Stefanie ; Prabakaran, Thaneas ; Reinert, Line S ; Mettenleiter, Thomas ; Chen, Zhijian J ; Knipe, David M ; Sandri-Goldin, Rozanne M ; Enquist, Lynn W ; Hartmann, Rune ; Mogensen, Trine H ; Rice, Stephen A ; Nyman, Tuula Anneli ; Matikainen, Sampsa ; Paludan, Søren R. / HSV‐1 ICP27 targets the TBK1‐activated STING signalsome to inhibit virus‐induced type I IFN expression. In: EMBO Journal. 2016 ; Vol. 2016, No. 35. pp. 1385-1399.
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title = "HSV‐1 ICP27 targets the TBK1‐activated STING signalsome to inhibit virus‐induced type I IFN expression",
abstract = "Herpes simplex virus (HSV) 1 stimulates type I IFN expression through the cGAS–STING–TBK1 signaling axis. Macrophages have recently been proposed to be an essential source of IFN during viral infection. However, it is not known how HSV‐1 inhibits IFN expression in this cell type. Here, we show that HSV‐1 inhibits type I IFN induction through the cGAS–STING–TBK1 pathway in human macrophages, in a manner dependent on the conserved herpesvirus protein ICP27. This viral protein was expressed de novo in macrophages with early nuclear localization followed by later translocation to the cytoplasm where ICP27 prevented activation of IRF3. ICP27 interacted with TBK1 and STING in a manner that was dependent on TBK1 activity and the RGG motif in ICP27. Thus, HSV‐1 inhibits expression of type I IFN in human macrophages through ICP27‐dependent targeting of the TBK1‐activated STING signalsome.",
keywords = "1182 Biochemistry, cell and molecular biology, HSV-1, luontainen immuniteetti, HSV-1, INNATE IMMUNE-RESPONSE, INNATE IMMUNITY, ICP27, IFN response",
author = "Christensen, {Maria H} and Jensen, {S{\o}ren B} and Miettinen, {Juho Jalmari} and Stefanie Luecke and Thaneas Prabakaran and Reinert, {Line S} and Thomas Mettenleiter and Chen, {Zhijian J} and Knipe, {David M} and Sandri-Goldin, {Rozanne M} and Enquist, {Lynn W} and Rune Hartmann and Mogensen, {Trine H} and Rice, {Stephen A} and Nyman, {Tuula Anneli} and Sampsa Matikainen and Paludan, {S{\o}ren R}",
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month = "7",
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language = "English",
volume = "2016",
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Christensen, MH, Jensen, SB, Miettinen, JJ, Luecke, S, Prabakaran, T, Reinert, LS, Mettenleiter, T, Chen, ZJ, Knipe, DM, Sandri-Goldin, RM, Enquist, LW, Hartmann, R, Mogensen, TH, Rice, SA, Nyman, TA, Matikainen, S & Paludan, SR 2016, 'HSV‐1 ICP27 targets the TBK1‐activated STING signalsome to inhibit virus‐induced type I IFN expression', EMBO Journal, vol. 2016, no. 35, pp. 1385-1399. https://doi.org/10.15252/embj.201593458

HSV‐1 ICP27 targets the TBK1‐activated STING signalsome to inhibit virus‐induced type I IFN expression. / Christensen, Maria H; Jensen, Søren B; Miettinen, Juho Jalmari; Luecke, Stefanie; Prabakaran, Thaneas; Reinert, Line S; Mettenleiter, Thomas; Chen, Zhijian J; Knipe, David M; Sandri-Goldin, Rozanne M; Enquist, Lynn W; Hartmann, Rune; Mogensen, Trine H; Rice, Stephen A; Nyman, Tuula Anneli; Matikainen, Sampsa; Paludan, Søren R.

In: EMBO Journal, Vol. 2016, No. 35, 27.07.2016, p. 1385-1399.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - HSV‐1 ICP27 targets the TBK1‐activated STING signalsome to inhibit virus‐induced type I IFN expression

AU - Christensen, Maria H

AU - Jensen, Søren B

AU - Miettinen, Juho Jalmari

AU - Luecke, Stefanie

AU - Prabakaran, Thaneas

AU - Reinert, Line S

AU - Mettenleiter, Thomas

AU - Chen, Zhijian J

AU - Knipe, David M

AU - Sandri-Goldin, Rozanne M

AU - Enquist, Lynn W

AU - Hartmann, Rune

AU - Mogensen, Trine H

AU - Rice, Stephen A

AU - Nyman, Tuula Anneli

AU - Matikainen, Sampsa

AU - Paludan, Søren R

N1 - DOI 10.15252/embj.201593458 Volume: Proceeding volume:

PY - 2016/7/27

Y1 - 2016/7/27

N2 - Herpes simplex virus (HSV) 1 stimulates type I IFN expression through the cGAS–STING–TBK1 signaling axis. Macrophages have recently been proposed to be an essential source of IFN during viral infection. However, it is not known how HSV‐1 inhibits IFN expression in this cell type. Here, we show that HSV‐1 inhibits type I IFN induction through the cGAS–STING–TBK1 pathway in human macrophages, in a manner dependent on the conserved herpesvirus protein ICP27. This viral protein was expressed de novo in macrophages with early nuclear localization followed by later translocation to the cytoplasm where ICP27 prevented activation of IRF3. ICP27 interacted with TBK1 and STING in a manner that was dependent on TBK1 activity and the RGG motif in ICP27. Thus, HSV‐1 inhibits expression of type I IFN in human macrophages through ICP27‐dependent targeting of the TBK1‐activated STING signalsome.

AB - Herpes simplex virus (HSV) 1 stimulates type I IFN expression through the cGAS–STING–TBK1 signaling axis. Macrophages have recently been proposed to be an essential source of IFN during viral infection. However, it is not known how HSV‐1 inhibits IFN expression in this cell type. Here, we show that HSV‐1 inhibits type I IFN induction through the cGAS–STING–TBK1 pathway in human macrophages, in a manner dependent on the conserved herpesvirus protein ICP27. This viral protein was expressed de novo in macrophages with early nuclear localization followed by later translocation to the cytoplasm where ICP27 prevented activation of IRF3. ICP27 interacted with TBK1 and STING in a manner that was dependent on TBK1 activity and the RGG motif in ICP27. Thus, HSV‐1 inhibits expression of type I IFN in human macrophages through ICP27‐dependent targeting of the TBK1‐activated STING signalsome.

KW - 1182 Biochemistry, cell and molecular biology

KW - HSV-1

KW - luontainen immuniteetti

KW - HSV-1

KW - INNATE IMMUNE-RESPONSE

KW - INNATE IMMUNITY

KW - ICP27

KW - IFN response

U2 - 10.15252/embj.201593458

DO - 10.15252/embj.201593458

M3 - Article

VL - 2016

SP - 1385

EP - 1399

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 35

ER -