RNA interference inhibits herpes simplex virus type 1 isolated from saliva samples and mucocutaneous lesions

Abstract

The aim of this study was to evaluate the use of RNA interference to inhibit herpes simplex virus type-1 replication in vitro. For herpes simplex virus type-1 gene silencing, three different small interfering RNAs (siRNAs) targeting the herpes simplex virus type-1 UL39 gene (sequence si-UL 39-1, si-UL 39-2, and si-UL 39-3) were used, which encode the large subunit of ribonucleotide reductase, an essential enzyme for DNA synthesis. Herpes simplex virus type-1 was isolated from saliva samples and mucocutaneous lesions from infected patients. All mucocutaneous lesions' samples were positive for herpes simplex virus type-1 by real-time PCR and by virus isolation; all herpes simplex virus type-1 from saliva samples were positive by real-time PCR and 50% were positive by virus isolation. The levels of herpes simplex virus type-1 DNA remaining after siRNA treatment were assessed by real-time PCR, whose results demonstrated that the effect of siRNAs on gene expression depends on siRNA concentration. The three siRNA sequences used were able to inhibit viral replication, assessed by real-time PCR and plaque assays and among them, the sequence si-UL 39-1 was the most effective. This sequence inhibited 99% of herpes simplex virus type-1 replication. The results demonstrate that silencing herpes simplex virus type-1 UL39 expression by siRNAs effectively inhibits herpes simplex virus type-1 replication, suggesting that siRNA based antiviral strategy may be a potential therapeutic alternative.

Inhibition of clinical pathogenic herpes simplex virus 1 strains with enzymatically created siRNA pools

“…Various approaches to prevent or treat HSV infections, such as vaccines, anti‐HSV antibodies, small molecule drugs, and chemically synthesized single‐site siRNAs, are currently under development [Palliser et al, ; Grosse et al, ; Belshe et al, ; Biswas et al, ; Silva et al, ; Krawczyk et al, ]. This study proposes the development of topical treatment of HSV infections using pools of HSV‐specific siRNA molecules and provides supportive evidence for the potential efficacy of this approach.…”

The Impact of Antiviral Resistance on Herpetic Keratitis

“…This activity results in a decreased viral load of HSV. 62 Other therapies have also shown efficacy in trials but are not FDA approved for HSK. Amentoflavone, a naturally occurring bioflavonoid, has shown promise in inhibiting rHSK in severe diseases.…”

siRNA intervention inhibiting viral replication and delivery strategies for treating herpes simplex viral infection

“…One study tested three siRNAs synthesized for targeting UL39 gene of HSV-1. One of the sequences was effective in inhibiting 99% replication of the HSV-1 infection [4]. siRNAs were also tested for their potential to control the herpetic encephalitis, induced by HSV-1 in mice model.…”