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In vitro and in vivo inhibition of rabies virus replication by RNA interference
Ono, Ekaterina A. Durymanova; Iamamoto, Keila; Castilho, Juliana G.; Carnieli Jr., Pedro; Oliveira, Rafael de Novaes; Achkar, Samira M.; Carrieri, Maria L.; Kotait, Ivanete; Brandão, Paulo E..
  • Ono, Ekaterina A. Durymanova; Universidade de São Paulo. Faculdade de Medicina Veterinária. São Paulo. BR
  • Iamamoto, Keila; Universidade de São Paulo. Faculdade de Medicina Veterinária. São Paulo. BR
  • Castilho, Juliana G.; Universidade de São Paulo. Faculdade de Medicina Veterinária. São Paulo. BR
  • Carnieli Jr., Pedro; Universidade de São Paulo. Faculdade de Medicina Veterinária. São Paulo. BR
  • Oliveira, Rafael de Novaes; Universidade de São Paulo. Faculdade de Medicina Veterinária. São Paulo. BR
  • Achkar, Samira M.; Universidade de São Paulo. Faculdade de Medicina Veterinária. São Paulo. BR
  • Carrieri, Maria L.; Universidade de São Paulo. Faculdade de Medicina Veterinária. São Paulo. BR
  • Kotait, Ivanete; Universidade de São Paulo. Faculdade de Medicina Veterinária. São Paulo. BR
  • Brandão, Paulo E.; Universidade de São Paulo. Faculdade de Medicina Veterinária. São Paulo. BR
Braz. j. microbiol ; 44(3): 879-882, July-Sept. 2013. tab
Article in English | LILACS | ID: lil-699783
ABSTRACT
Rabies is a zoonotic disease that affects all mammals and leads to more than 55,000 human deaths every year, caused by rabies virus (RABV) (Mononegavirales Rhabdoviridae Lyssavirus). Currently, human rabies treatment is based on the Milwaukee Protocol which consists on the induction of coma and massive antiviral therapy. The aim of this study was to assess the decrease in the titer of rabies virus both in vitro and in vivo using short-interfering RNAs. To this end, three siRNAs were used with antisense strands complementary to rabies virus nucleoprotein (N) mRNA. BHK-21 cells monolayers were infected with 1000 to 0.1 TCID50 of PV and after 2 hours the cells were transfected with each of tree RNAs in separate using Lipofectamine-2000. All three siRNAs reduced the titer of PV strain in a least 0.72 logTCID50/mL and no cytotoxic effect was observed in the monolayers treated with Lipofectamine-2000. Swiss albino mice infected with 10.000 to 1 LD of PV strain by the intracerebral route were also transfected after two hours of infection with a pool 3 siRNAs with Lipofectamine-2000 by the intracerebral route, resulting in a survival rate of 30% in mice inoculated with 100 LD50, while the same dose led to 100% mortality in untreated animals. Lipofectamine-2000 showed no toxic effect in control mice. These results suggest that intracerebral administration of siRNAs might be an effective antiviral strategy for rabies.
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Full text: Available Index: LILACS (Americas) Main subject: Antiviral Agents / Rabies / Rabies virus / Virus Replication / RNA, Small Interfering / RNA Interference Type of study: Practice guideline Limits: Animals Language: English Journal: Braz. j. microbiol Journal subject: Microbiology Year: 2013 Type: Article / Project document Affiliation country: Brazil Institution/Affiliation country: Universidade de São Paulo/BR

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Full text: Available Index: LILACS (Americas) Main subject: Antiviral Agents / Rabies / Rabies virus / Virus Replication / RNA, Small Interfering / RNA Interference Type of study: Practice guideline Limits: Animals Language: English Journal: Braz. j. microbiol Journal subject: Microbiology Year: 2013 Type: Article / Project document Affiliation country: Brazil Institution/Affiliation country: Universidade de São Paulo/BR