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

Research output: Contribution to journalArticle

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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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Japanese Encephalitis Virus
Medulloblastoma
Genes
Chi-Square Distribution
Infection
Ubiquitins
STAT1 Transcription Factor
Students
Flavivirus
Viral Genome
Central Nervous System Diseases
Response Elements
Culicidae
Luciferases
Crowns
Interleukin-8
Interferons
Antiviral Agents

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Virology

Cite this

Hsiao, Nai-Wan ; Chen, Jiun Wei ; Yang, Tsuey Ching ; Orloff, Gregg M. ; Wu, Yi Ying ; Lai, Chih Ho ; Lan, Yu Ching ; Lin, Cheng Wen. / ISG15 over-expression inhibits replication of the Japanese encephalitis virus in human medulloblastoma cells. In: Antiviral Research. 2010 ; Vol. 85, No. 3. pp. 504-511.
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ISG15 over-expression inhibits replication of the Japanese encephalitis virus in human medulloblastoma cells. / Hsiao, Nai-Wan; Chen, Jiun Wei; Yang, Tsuey Ching; Orloff, Gregg M.; Wu, Yi Ying; Lai, Chih Ho; Lan, Yu Ching; Lin, Cheng Wen.

In: Antiviral Research, Vol. 85, No. 3, 01.03.2010, p. 504-511.

Research output: Contribution to journalArticle

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