Effects of RNA interference therapy against herpes simplex virus type 1 encephalitis.
| Autor: | da Silva AS; Laboratory of Viral Technology Development, Oswaldo Cruz Institute/Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. alesantosbio@yahoo.com.br., Raposo JV, Pereira TC, Pinto MA, de Paula VS |
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| Jazyk: | angličtina |
| Zdroj: | Antiviral therapy [Antivir Ther] 2016; Vol. 21 (3), pp. 225-35. Date of Electronic Publication: 2015 Dec 15. |
| DOI: | 10.3851/IMP3016 |
| Abstrakt: | 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. |
| Databáze: | MEDLINE |
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