Inhibition of herpes simplex virus type 1 by small interfering RNA.
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.


OBJECTIVE
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.


CONCLUSIONS
: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.
Zhang
Y Q
YQ
Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Lai
W
W
Li
H
H
Li
G
G
D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D006561:Herpes Simplex / Q000628:therapy*; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000138:chemical synthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014709:Vero Cells; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000235:genetics*
D034741:RNA, Small Interfering