HSV Infection Induces Production of ROS, which Potentiate Signaling from Pattern Recognition Receptors: Role for S-glutathionylation of TRAF3 and 6

• DOI: 10.1371/journal.ppat.1002250
• Publication Date: 2011-09-16T04:31:12Z
• Authors: Regina Gonzalez-D...; Kristy A. Horan; Stine H. Rahbek; Hidenori Ichijo; Zhijian J. Chen; John J. Mieyal; Rune Hartmann; Søren R. Paludan
• Keywords: 0301 basic medicine; QH301-705.5; Mice; 03 medical and health sciences; Animals; Simplexvirus; Biology (General); RNA, Small Interfering; TNF Receptor-Associated Factor 6; TNF Receptor-Associated Factor 3; NF-kappa B; Herpes Simplex; RC581-607; Glutathione; Immunity, Innate; 3. Good health; Mice, Inbred C57BL; Receptors, Pattern Recognition; Interferon Type I; Cytokines; Interferon Regulatory Factor-3; RNA Interference; Immunologic diseases. Allergy; Chemokines; Reactive Oxygen Species; Research Article; Signal Transduction

The innate immune response constitutes the first line of defense against infections. Pattern recognition receptors recognize pathogen structures and trigger intracellular signaling pathways leading to cytokine chemokine expression. Reactive oxygen species (ROS) are emerging as an important regulator some these pathways. ROS directly interact with components or induce other post-translational modifications such S-glutathionylation, thereby altering target function. Applying live microscopy, we have demonstrated that herpes simplex virus (HSV) infection induces early production required for activation NF-κB IRF-3 type I IFNs ISGs. All known involved in HSV were shown be dependent on cellular redox levels successful signaling. In addition, provide biochemical evidence suggesting S-glutathionylation TRAF family proteins important. particular, by performing mutational studies show a conserved cysteine residue TRAF3 TRAF6 is ROS-dependent conclusion, findings demonstrate essential effective infection.