Inhibition of herpes simplex virus type 1 by small interfering RNA

Zhang, Y. Q.; Lai, W.; Li, H.; Li, G.

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 ∼85% and ∼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.