Nucleic Acid-Based Immune System: the Antiviral Potential of Mammalian RNA Silencing

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Abstract
RNAi, also known as RNA silencing or posttranscriptional gene silencing, is a process that responds to double-stranded RNA (dsRNA) by silencing gene expression in a sequence-specific manner. The RNAi machinery uses dsRNA duplexes as guides to target and destroy specific cellular or viral RNAs. RNA silencing was initially described in plants more than a decade ago (reviewed in reference 62). Overexpression of transgenes in plants can result in cosuppression of homologous endogenous genes (43, 63). Also, infection by plant RNA viruses can be restricted or prevented by the artificial expression of pieces of the viral genomic RNA. This resistant state appears to be mediated by a cytoplasmic activity that targets specific RNAs for inactivation (38). It was thus proposed that suppression of endogenous genes or resistance to RNA viruses could arise from a sequence-specific RNA degradation system. Similar mechanisms were invoked to explain the phenomenon of cross-protection in which a nonpathogenic strain of plant virus elicits resistance to a related pathogenic virus (reviewed in reference 53). Furthermore, it was observed that cellular genes carried by viruses could lead to decreased expression of cognate endogenous host genes, an occurrence that was suggested to be mediated by the same mechanism responsible for virus resistance and which was named virus-induced gene silencing (33).