HSV-1 ICP27 targets the TBK1-activated STING signalsome to inhibit virus-induced type I IFN expression. Author Maria Christensen, Søren Jensen, Juho Miettinen, Stefanie Luecke, Thaneas Prabakaran, Line Reinert, Thomas Mettenleiter, Zhijian Chen, David Knipe, Rozanne Sandri-Goldin, Lynn Enquist, Rune Hartmann, Trine Mogensen, Stephen Rice, Tuula Nyman, Sampsa Matikainen, Søren Paludan Publication Year 2016 Type Journal Article 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 Humans, Membrane Proteins, Cells, Cultured, Host-Pathogen Interactions, Interferon Type I, Immune Evasion, Herpesvirus 1, Human, Protein Interaction Mapping, Immediate-Early Proteins, Macrophages, Protein Serine-Threonine Kinases Journal EMBO J Volume 35 Issue 13 Pages 1385-99 Date Published 2016 Jul 01 ISSN Number 1460-2075 DOI 10.15252/embj.201593458 Alternate Journal EMBO J PMCID PMC4931188 PMID 27234299 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML