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

Maria H. Christensen; Søren B. Jensen; Juho J. 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 A. Nyman; Sampsa Matikainen; Søren R. Paludan

doi:10.15252/embj.201593458

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

Maria H. Christensen, Søren B. Jensen, Juho J. 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 A. Nyman, Sampsa Matikainen, Søren R. Paludan^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

187 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	EMBO Journal
Vol/bind	35
Nummer	13
Sider (fra-til)	1385-1399
Antal sider	15
ISSN	0261-4189
DOI	https://doi.org/10.15252/embj.201593458
Status	Udgivet - 1 jul. 2016

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Christensen, M. H., Jensen, S. B., Miettinen, J. J., Luecke, S., Prabakaran, T., Reinert, L. S., Mettenleiter, T., Chen, Z. J., Knipe, D. M., Sandri-Goldin, R. M., Enquist, L. W., Hartmann, R., Mogensen, T. H., Rice, S. A., Nyman, T. A., Matikainen, S., & Paludan, S. R. (2016). HSV-1 ICP27 targets the TBK1-activated STING signalsome to inhibit virus-induced type I IFN expression. EMBO Journal, 35(13), 1385-1399. https://doi.org/10.15252/embj.201593458

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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 = "herpes simplex virus, immune evasion, innate immunity, type I IFN",

author = "Christensen, {Maria H.} and Jensen, {S{\o}ren B.} and Miettinen, {Juho J.} 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 A.} and Sampsa Matikainen and Paludan, {S{\o}ren R.}",

note = "Publisher Copyright: {\textcopyright} 2016 The Authors",

year = "2016",

month = jul,

day = "1",

doi = "10.15252/embj.201593458",

language = "English",

volume = "35",

pages = "1385--1399",

journal = "EMBO Journal",

issn = "0261-4189",

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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, bind 35, nr. 13, s. 1385-1399. https://doi.org/10.15252/embj.201593458

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 J.

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 A.

AU - Matikainen, Sampsa

AU - Paludan, Søren R.

PY - 2016/7/1

Y1 - 2016/7/1

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 - herpes simplex virus

KW - immune evasion

KW - innate immunity

KW - type I IFN

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U2 - 10.15252/embj.201593458

DO - 10.15252/embj.201593458

M3 - Journal article

C2 - 27234299

AN - SCOPUS:85027918711

SN - 0261-4189

VL - 35

SP - 1385

EP - 1399

JO - EMBO Journal

JF - EMBO Journal

IS - 13

ER -

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

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