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

TitleHSV-1 ICP27 targets the TBK1-activated STING signalsome to inhibit virus-induced type I IFN expression.
Publication TypeJournal Article
Year of Publication2016
AuthorsChristensen, 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
JournalEMBO J
Volume35
Issue13
Pagination1385-99
Date Published2016 Jul 01
ISSN1460-2075
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.

DOI10.15252/embj.201593458
Alternate JournalEMBO J.
PubMed ID27234299
PubMed Central IDPMC4931188
Grant ListR01 AI106934 / AI / NIAID NIH HHS / United States