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Virus Genes ; 38(2): 224-31, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19169857

RESUMEN

RNA interference (RNAi) is a process that is induced by double stranded RNA and involves the degradation of specific sequences of mRNA in the cytoplasm of the eukaryotic cells. It has been used as an antiviral tool against many viruses, including flaviviruses. The genus Flavivirus contains the most important arboviruses in the world, i.e., dengue (DENV) and yellow fever (YFV). In our study, we investigated the in vitro and in vivo effect of RNAi against YFV. Using stable cell lines that expressed RNAi against YFV, the cell lines were able to inhibit as much as 97% of the viral replication. Two constructions (one against NS1 and the other against E region of YFV genome) were able to protect the adult Balb/c mice against YFV challenge. The histopathologic analysis demonstrated an important protection of the central nervous system by RNAi after 10 days of viral challenge. Our data suggests that RNAi is a potential viable therapeutic weapon against yellow fever.


Asunto(s)
Antivirales/uso terapéutico , Interferencia de ARN , ARN Interferente Pequeño/uso terapéutico , Replicación Viral , Fiebre Amarilla/tratamiento farmacológico , Virus de la Fiebre Amarilla/efectos de los fármacos , Virus de la Fiebre Amarilla/fisiología , Animales , Antivirales/farmacología , Sistema Nervioso Central/patología , Chlorocebus aethiops , Ratones , Ratones Endogámicos BALB C , ARN Interferente Pequeño/farmacología , Análisis de Supervivencia , Células Vero , Proteínas del Envoltorio Viral/antagonistas & inhibidores , Proteínas del Envoltorio Viral/genética , Proteínas no Estructurales Virales/antagonistas & inhibidores , Proteínas no Estructurales Virales/genética , Fiebre Amarilla/patología , Virus de la Fiebre Amarilla/genética
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