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EMBO J. 2016 Jul 1;35(13):1385-99. doi: 10.15252/embj.201593458. Epub 2016 May 27.

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

Author information

1
Department of Biomedicine, University of Aarhus, Aarhus, Denmark Aarhus Research Center for Innate Immunology, University of Aarhus, Aarhus, Denmark.
2
University of Helsinki, Helsinki, Finland.
3
Friedrich-Loeffler-Institut, Insel Riems, Germany.
4
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
5
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
6
Department of Microbiology & Molecular Genetics, University of California, Irvine, CA, USA.
7
Princeton University, Princeton, NJ, USA.
8
Department of Biomedicine, University of Aarhus, Aarhus, Denmark Aarhus Research Center for Innate Immunology, University of Aarhus, Aarhus, Denmark Department of Molecular Biology and Genetics, Aarhus Research Center for Innate Immunity, Aarhus University, Aarhus, Denmark.
9
Department of Biomedicine, University of Aarhus, Aarhus, Denmark Aarhus Research Center for Innate Immunology, University of Aarhus, Aarhus, Denmark Aarhus University Hospital Skejby, Aarhus, Denmark.
10
Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN, USA.
11
Finnish Institute of Occupational Health, Helsinki, Finland.
12
Department of Biomedicine, University of Aarhus, Aarhus, Denmark Aarhus Research Center for Innate Immunology, University of Aarhus, Aarhus, Denmark srp@biomed.au.dk.

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

PMID:
27234299
PMCID:
PMC4931188
DOI:
10.15252/embj.201593458
[Indexed for MEDLINE]
Free PMC Article

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