title: Effects of RNA interference therapy against herpes simplex virus type 1 encephalitis.
abstract: Herpetic encephalitis (HSE) is caused mainly by herpes simplex virus type 1 (HSV-1) with an annual incidence of 1-4 cases/million inhabitants. Currently, HSE treatment faces difficulties such as the use of antivirals with elevated toxicity, metabolic side effects and HSV-1 resistance. An alternative to antivirals is the use of small interfering RNA (siRNA) as a viral replication inhibitor. In this work, siRNA targeting the UL-39 region was evaluated for HSE treatment in vivo.
  
  
  
  BALB/c mice were inoculated with HSV-1 and treated with siRNA. The treatment was evaluated through kinetics of HSV-1 replication inhibition, number of siRNA doses administered and treatment with siRNA plus acyclovir. All groups were evaluated for signs of HSE, mortality and HSV-1 replication inhibition.
  
  
  
  The treated group of the kinetic experiment demonstrated a reduction of HSE signs and an HSV-1 replication inhibition of 43.6-99.9% in the brain and 53-98% in trigeminal ganglia (TG). Animals treated with one or two doses of siRNA had a prolonged survival time, reduced clinical signs of HSE and HSV-1 replication inhibition of 67.7% in brains and 85.7% in TG of animals treated with two doses of siRNA. Also, animals treated with siRNA plus acyclovir demonstrated reduced signs of HSE and mortality, as well as HSV-1 replication inhibition in the brain (83.2%) and TG (74.5%).
  
  
  
  These findings demonstrated that siRNA was capable of reducing HSE clinical signs, prolonging survival time and inhibiting HSV-1 replication in mice. Thus, siRNA can be a potential alternative to the standard HSE treatment especially to reduce clinical signs and extend survival time in vivo.
authors.affiliation: Laboratory of Viral Technology Development, Oswaldo Cruz Institute/Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. alesantosbio@yahoo.com.br.
authors.forename: Alexandre S
authors.initials: AS
authors.lastname: da Silva
authors.forename: Jéssica V
authors.initials: JV
authors.lastname: Raposo
authors.forename: Tiago C
authors.initials: TC
authors.lastname: Pereira
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Pinto
authors.forename: Vanessa S
authors.initials: VS
authors.lastname: de Paula
mesh_terms: D000818:Animals; D020803:Encephalitis, Herpes Simplex / Q000628:therapy* / Q000821:virology; D015316:Genetic Therapy; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D034622:RNA Interference; D034741:RNA, Small Interfering; D014779:Virus Replication / Q000235:genetics*
chemical_list: D034741:RNA, Small Interfering