Hsv infection induces production of ros, which potentiate signaling from pattern recognition receptors

Role for s-glutathionylation of traf3 and 6

Regina Gonzalez-Dosal, Kristy A. Horan, Stine H. Rahbek, Hidenori Ichijo, Zhijian J. Chen, John J. Mieyal, Rune Hartmann, Søren R. Paludan

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

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

Original languageEnglish (US)
Article numbere1002250
JournalPLoS Pathogens
Volume7
Issue number9
DOIs
StatePublished - Sep 2011

Fingerprint

Pattern Recognition Receptors
Reactive Oxygen Species
Simplexvirus
Infection
Virus Diseases
Innate Immunity
TNF Receptor-Associated Factor 3
TNF Receptor-Associated Factor 6
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Post Translational Protein Processing
Chemokines
Oxidation-Reduction
Cysteine
Microscopy
Cytokines

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Hsv infection induces production of ros, which potentiate signaling from pattern recognition receptors : Role for s-glutathionylation of traf3 and 6. / Gonzalez-Dosal, Regina; Horan, Kristy A.; Rahbek, Stine H.; Ichijo, Hidenori; Chen, Zhijian J.; Mieyal, John J.; Hartmann, Rune; Paludan, Søren R.

In: PLoS Pathogens, Vol. 7, No. 9, e1002250, 09.2011.

Research output: Contribution to journalArticle

Gonzalez-Dosal, Regina ; Horan, Kristy A. ; Rahbek, Stine H. ; Ichijo, Hidenori ; Chen, Zhijian J. ; Mieyal, John J. ; Hartmann, Rune ; Paludan, Søren R. / Hsv infection induces production of ros, which potentiate signaling from pattern recognition receptors : Role for s-glutathionylation of traf3 and 6. In: PLoS Pathogens. 2011 ; Vol. 7, No. 9.
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