ISG15 over-expression inhibits replication of the Japanese encephalitis virus in human medulloblastoma cells

Nai Wan Hsiao, Jiun Wei Chen, Tsuey Ching Yang, Gregg M. Orloff, Yi Ying Wu, Chih Ho Lai, Yu Ching Lan, Cheng Wen Lin

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Abstract

IFN-stimulated gene 15 (ISG15), an ubiquitin-like protein, is rapidly induced by IFN-α/β, and ISG15 conjugation is associated with the antiviral immune response. Japanese encephalitis virus (JEV), a mosquito-borne neurotropic flavivirus, causes severe central nervous system diseases. We investigated the potential anti-JEV effect of ISG15 over-expression. ISG15 over-expression in human medulloblastoma cells significantly reduced the JEV-induced cytopathic effect and inhibited JEV replication by reducing the viral titers and genomes (p < 0.05, Student's t-test); it also increased activation of the interferon stimulatory response element (ISRE)-luciferase cis-acting reporter in JEV-infected cells (p < 0.05, Chi-square test). Furthermore, Western blotting revealed that ISG15 over-expression increased phosphorylation of IRF-3 (Ser396), JAK2 (Tyr1007/1008) and STAT1 (Tyr701 and Ser727) in JEV-infected cells (P < 0.05, Chi-square test). Confocal imaging indicated that nucleus translocation of transcription factor STAT1 occurred in ISG15-over-expressing cells but not in vector control cells post-JEV infection. ISG15 over-expression activated the expression of STAT1-dependent genes including IRF-3, IFN-β, IL-8, PKR and OAS before and post-JEV infection (p = 0.063, Student's t-test). The results enabled elucidation of the molecular mechanism of ISG15 over-expression against JEV, which will be useful for developing a novel treatment to combat JEV infection. Crown

Original languageEnglish
Pages (from-to)504-511
Number of pages8
JournalAntiviral Research
Volume85
Issue number3
DOIs
Publication statusPublished - 2010 Mar 1

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Virology

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