PMID- 26669609
OWN - NLM
STAT- MEDLINE
DCOM- 20180118
LR  - 20180511
IS  - 2040-2058 (Electronic)
IS  - 1359-6535 (Linking)
VI  - 21
IP  - 3
DP  - 2016
TI  - Effects of RNA interference therapy against herpes simplex virus type 1 
      encephalitis.
PG  - 225-35
LID - 10.3851/IMP3016 [doi]
AB  - BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.
FAU - da Silva, Alexandre S
AU  - da Silva AS
AD  - Laboratory of Viral Technology Development, Oswaldo Cruz Institute/Oswaldo Cruz 
      Foundation, Rio de Janeiro, Brazil. alesantosbio@yahoo.com.br.
FAU - Raposo, Jessica V
AU  - Raposo JV
FAU - Pereira, Tiago C
AU  - Pereira TC
FAU - Pinto, Marcelo A
AU  - Pinto MA
FAU - de Paula, Vanessa S
AU  - de Paula VS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151215
PL  - England
TA  - Antivir Ther
JT  - Antiviral therapy
JID - 9815705
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Animals
MH  - Encephalitis, Herpes Simplex/*therapy/virology
MH  - Genetic Therapy
MH  - Herpesvirus 1, Human/genetics/*physiology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - *RNA Interference
MH  - *RNA, Small Interfering
MH  - Virus Replication/*genetics
EDAT- 2015/12/17 06:00
MHDA- 2018/01/19 06:00
CRDT- 2015/12/17 06:00
PHST- 2015/09/29 00:00 [accepted]
PHST- 2015/12/17 06:00 [entrez]
PHST- 2015/12/17 06:00 [pubmed]
PHST- 2018/01/19 06:00 [medline]
AID - 10.3851/IMP3016 [doi]
PST - ppublish
SO  - Antivir Ther. 2016;21(3):225-35. doi: 10.3851/IMP3016. Epub 2015 Dec 15.