Inhibition of herpes simplex virus type 1 by small interfering RNA

Clin Exp Dermatol. 2008 Jan;33(1):56-61. doi: 10.1111/j.1365-2230.2007.02543.x. Epub 2007 Nov 2.

Abstract

Background: RNA interference, a conserved mechanism in which a sequence-specific gene-silencing process is mediated by small interfering RNA (siRNA), is a promising method of gene therapy in treating a variety of viral diseases.

Aim: To investigate the antiviral effects of siRNA on herpes simplex virus type 1 (HSV-1) replication in Vero cells.

Methods: The antiviral effects of siRNA duplexes targeting the VP16 and DNA polymerase genes of HSV-1 were evaluated by yield-reduction and plaque-reduction assays. The effect of siRNA on the expression of target genes was measured by real-time quantitative reverse transcription PCR.

Results: Two siRNA duplexes (siRNA-1, targeting VP16, and siRNA-4, targeting DNA polymerase), were found to be highly effective in inhibiting HSV-1 replication. siRNA-1 and siRNA-4 reduced HSV-1 replication by around 2 log(10) and 1 log(10) in the yield--reduction assay and by approximately 85% and approximately 70% in the plaque-reduction assay, respectively. Significant decreases in the mRNA level of VP16 and DNA polymerase genes were detected after viral infection in the Vero cells pretreated with siRNA-1 and siRNA-4, respectively.

Conclusion: :These results indicate that siRNA can potently inhibit HSV-1 replication in vitro, suggesting that siRNA-based antiviral therapy may be a potential effective therapeutic alternative for patients with HSV-1 infection.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Cells, Cultured
  • Chlorocebus aethiops
  • Gene Expression Regulation
  • Herpes Simplex / therapy*
  • Herpesvirus 1, Human / drug effects
  • Herpesvirus 1, Human / genetics*
  • RNA Interference*
  • RNA, Small Interfering / chemical synthesis
  • RNA, Small Interfering / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Vero Cells
  • Viral Plaque Assay
  • Virus Replication / genetics*

Substances

  • RNA, Small Interfering