Application of shRNA-containing herpes simplex virus type 1 (HSV-1)-based gene therapy for HSV-2-induced genital herpes

J Virol Methods. 2013 Nov;193(2):353-8. doi: 10.1016/j.jviromet.2013.06.037. Epub 2013 Jul 8.

Abstract

HSV-1-based vectors have been widely used to achieve targeted delivery of genes into the nervous system. In the current study, we aim to use shRNA-containing HSV-1-based gene delivery system for the therapy of HSV-2 infection. Guinea pigs were infected intravaginally with HSV-2 and scored daily for 100 days for the severity of vaginal disease. HSV-2 shRNA-containing HSV-1 was applied intravaginally daily between 8 and 14 days after HSV-2 challenge. Delivery of HSV-2 shRNA-containing HSV-1 had no effect on the onset of disease and acute virus shedding in animals, but resulted in a significant reduction in both the cumulative recurrent lesion days and the number of days with recurrent disease. Around half of the animals in the HSV-2 shRNA group did not develop recurrent disease 100 days post HSV-2 infection. In conclusion, HSV-2 shRNA-containing HSV-1 particles are effective in reducing the recurrence of genital herpes caused by HSV-2.

Keywords: Genital herpes; Herpes simplex virus type 1 (HSV-1) vector; Herpes simplex virus type 2 (HSV-2).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Genetic Therapy / methods*
  • Guinea Pigs
  • Herpes Genitalis / pathology
  • Herpes Genitalis / therapy*
  • Herpes Genitalis / virology
  • Herpesvirus 1, Human / genetics*
  • Herpesvirus 2, Human / genetics*
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / therapeutic use*
  • Severity of Illness Index
  • Time Factors
  • Vagina / virology
  • Virus Shedding

Substances

  • RNA, Small Interfering