Abstract
Keratinocytes are important for the acute phase of HSV-1 infection and subsequent persistence in sensory nervous tissue. In this study, we showed that keratinocytes (HEL-30) were refractory to IFN-γ induction of an antiviral state to HSV-1 infection, while IFN-γ did induce an antiviral state in fibroblasts (L929). This led us to examine the possible role of suppressor of cytokine signaling-1 (SOCS-1) in this refractiveness. RT-PCR analysis of SOCS-1 mRNA expression in HSV-1-infected cells showed a 4-fold increase for keratinocytes while having a negligible effect on fibroblasts. A similar pattern was observed at the level of SOCS-1 protein induction. Activation of STAT1α in keratinocytes was inhibited by HSV-1 infection. A direct effect of HSV-1 on the SOCS-1 promoter was shown in a luciferase reporter gene assay. We have developed a small peptide antagonist of SOCS-1, pJAK2(1001–1013), that had both an antiviral effect in keratinocytes against HSV-1 as well as a synergistic effect on IFN-γ induction of an antiviral state. HSV-1 ICP0 mutant was inhibited by IFN-γ in HEL-30 cells and was less effective than wild-type virus in induction of SOCS-1 promoter. We conclude that SOCS-1 plays an important role in the inhibition of the antiviral effect of IFN-γ in keratinocytes infected with HSV-1. The use of SOCS-1 antagonist to abrogate this refractiveness could have a transformational effect on therapy against viral infections.
Original language | English |
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Pages (from-to) | 1253-1262 |
Number of pages | 10 |
Journal | Journal of Immunology |
Volume | 183 |
Issue number | 2 |
DOIs | |
State | Published - Jul 15 2009 |
ASJC Scopus Subject Areas
- Immunology and Allergy
- Immunology
Keywords
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Cell Line, Tumor
- Herpesvirus 1, Human / immunology*
- Herpesvirus 1, Human / pathogenicity
- Humans
- Immunity
- Interferon-Stiumlated Gene Factor 3 / antagonists & inhibitors
- Interferon-gamma / immunology
- Keratinocytes / metabolism
- Keratinocytes / virology*
- Peptides / pharmacology
- Promotor Regions, Genetic
- RNA, Messenger / analysis
- Suppressor of Cytokine Signaling 1 Protein
- Suppressor of Cytokine Signaling Proteins / antagonists & inhibitors
- Suppressor of Cytokine Signaling Proteins / genetics*
- Inferon-Stimulated Gene Factor 3
- Peptides
- RNA, Messenger
- SOCS1 protein, human
- gamma interferon activation factor
- Interferon-gamma
Disciplines
- Medical Cell Biology
- Medical Neurobiology
- Medical Physiology
- Neurosciences
- Physiological Processes