Inhibition of γ-secretase Cleavage in the Notch Signaling Pathway Blocks HSV-2-induced Type I and Type II Interferon Production

Overview

Journal Viral Immunol

Specialties Allergy & Immunology
Microbiology

Date 2010 Dec 15

PMID 21142451

Citations 4

Authors

Alexandra Svensson

Emely Jakara

Andrey Shestakov

Kristina Eriksson

Affiliations

Soon will be listed here.

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.

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