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HSV-1-Induced SOCS-1 Expression in Keratinocytes: Use of a SOCS-1 Antagonist to Block a Novel Mechanism of Viral Immune Evasion
The Journal of Immunology
  • Kenneth G. Frey
  • Chulbul M. I. Ahmed
  • Rea Dabelic
  • Lindsey D. Jager
  • Ezra N. Noon-Song
  • S. Mohammad Haider
  • Howard M. Johnson
  • Nancy J. Bigley, Wright State University - Main Campus
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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.
Citation Information
Kenneth G. Frey, Chulbul M. I. Ahmed, Rea Dabelic, Lindsey D. Jager, et al.. "HSV-1-Induced SOCS-1 Expression in Keratinocytes: Use of a SOCS-1 Antagonist to Block a Novel Mechanism of Viral Immune Evasion" The Journal of Immunology Vol. 183 Iss. 2 (2009) p. 1253 - 1262 ISSN: 0022-1767
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