title: Inhibition of γ-secretase cleavage in the notch signaling pathway blocks HSV-2-induced type I and type II interferon production.
abstract: We have evaluated the role of γ-secretase, which is a crucial component in the Notch-induced signaling cascade, on herpes simplex virus type 2 (HSV-2)-induced innate and acquired interferon responses in human CD4(+) T cells and plasmacytoid dendritic cells (pDC). We found that blockade of the Notch signaling pathway with a pharmacological γ-secretase inhibitor blocked both HSV-2-induced interferon-γ (IFN-γ) production in CD4(+) T cells, and HSV-2-induced IFN-α production in pDC in a dose-dependent fashion. These effects were not due to an overall suppressive capacity of the γ-secretase inhibitor, as it affected neither phytohemagglutinin (PHA)-induced IFN-γ production in CD4(+) T cells, nor CpG-induced IFN-α production in pDC. Our data suggest that Notch signaling could be involved in HSV-2-induced interferon responses in CD4(+) T-cells and pDC.
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden. alexandra.svensson@microbio.gu.se
authors.forename: Alexandra
authors.initials: A
authors.lastname: Svensson
authors.forename: Emely
authors.initials: E
authors.lastname: Jäkärä
authors.forename: Andrey
authors.initials: A
authors.lastname: Shestakov
authors.forename: Kristina
authors.initials: K
authors.lastname: Eriksson
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000276:immunology*; D001570:Benzodiazepinones / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D006558:Herpes Genitalis / Q000276:immunology; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis*; D051880:Receptors, Notch / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: C529132:2-(((3,5-difluorophenyl)acetyl)amino)-N-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl)propanamide; D001570:Benzodiazepinones; D004791:Enzyme Inhibitors; D007370:Interferon Type I; D051880:Receptors, Notch; D007371:Interferon-gamma; D053829:Amyloid Precursor Protein Secretases