Herpes Simplex Virus I Obstucts the Type II Interferon Pathway in Keratinocytes by Induction of Suppressor of Cytokine Synthesis-1 (94.9)

Abstract

Abstract Herpesviruses are masters at evading the immune system. HSV-1 employs a variety of strategies to blunt the immune response, for example, downregulation of expression of class I MHC molecules. Studies using mouse L929 fibroblasts and HEL-30 keratinocytes revealed a differential response to treatment with interferon-γ (IFN-γ). L929 cells were protected from HSV-1-induced lysis by pretreatment with IFN-γ while HEL-30 cells were not. Interestingly, treatment of HEL-30 cell with IFN-γ followed by HSV-1 infection led to a 14-fold increase in SOCS-1 transcripts while treatment with IFN-γ alone increased SOCS-1 by 7-fold, while in comparison L929 cells showed much less increase in SOCS-1. Recent evidence indicates that HSV-1 inhibits the interferon pathway. SOCS-1 is the primary negative regulator of signaling by IFN-γ via the JAK/STAT pathway. Here we establish that infection of HEL-30 cells with HSV-1 (syn 17+) leads to a rapid induction of SOCS-1 at both transcript and protein levels. This induction is evident as early as 2 hours p.i., and is stable up to 8 hours p.i. Use of siRNA against SOCS-1 indicates that knockdown of SOCS-1 prior to treatment with IFN-γ results in inhibition of HSV-1 replication. These results suggest a possible therapeutic strategy to herpes infection by treatment with SOCS-1 siRNA and IFN-γ.