Silencing viruses by RNA interference - PubMed (original) (raw)

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Silencing viruses by RNA interference

Florence Colbère-Garapin et al. Microbes Infect. 2005 Apr.

Abstract

Post-transcriptional gene silencing (PTGS) makes possible new approaches for studying the various steps of the viral cycle. Plus-strand RNA viruses appear to be attractive targets for small interfering RNAs (siRNAs), as their genome functions as both mRNA and replication template. PTGS creates an alternative to classic reverse genetics for viruses with either negative-strand or double-stranded RNA genomes and for those with a large genome. PTGS allows modification of the expression of a given cellular gene as a means to elucidate its role in the viral cycle and in virus-host cell interactions, and to investigate cellular pathways involved in viral pathogenesis. It also allows the creation of new animal models of human diseases. In addition, PTGS already appears to be a promising new therapeutic tool to fight viral multiplication and dissemination through the host and to prevent inflammation and virus-induced pathogenesis, including virus-induced tumorigenesis.

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Figures

Fig. 1

Fig. 1

A schematic model of gene silencing by synthetic siRNAs. Once transfected into cells, synthetic siRNAs are phosphorylated, and a helicase, which may be associated with the RISC, leads to siRNA unwinding. The antisense strand of siRNA guides the complex towards the cognate mRNA. The target RNA is cleaved by an endoribonuclease in the RISC in a homology-dependent manner, resulting in mRNA degradation (see , and references in the text).

Fig. 2

Fig. 2

Schematic representation of the multiplication cycle of an RNA+ virus with potential siRNA targets. Silencing cellular mRNAs encoding proteins involved in viral multiplication is illustrated on the left-hand side of the figure, and silencing viral RNAs is illustrated on the right-hand side of the figure.

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