Trends in Genetics
ReviewRNA silencing as a plant immune system against viruses
Section snippets
A generalized response to viruses
For decades, the prophylactic inoculation of attenuated viral strains has been used to control viral diseases in plants. The rationale for this form of vaccination, called ‘cross-protection’, came from classic observations that many infections in plants prevent the secondary accumulation of viral strains that are closely related to the primary-infecting virus 8. For several plant viruses, the mechanism underlying cross-protection is a post-transcriptional and RNA-mediated process that targets
Viral-encoded suppressors of RNA silencing
The simple observation that viruses infect plants at all highlights the fact that they have somehow evolved to avoid or suppress the host RNA silencing response. This idea was first prompted by the demonstration that co-inoculation of a normally innocuous virus with potyviruses leads to an extreme accentuation of symptoms caused by high accumulation of the non-potyviral partner. It was shown that this synergism results from suppression, by the Hc-protease (HcPro) of potyviruses, of a host
Initiation: a central role for double-stranded RNA
Transgene constructs engineered to produce dsRNA as opposed to single-stranded (ss) RNA cause a high incidence of RNA silencing in plants 28, 29, consistent with the demonstration that dsRNA is sufficient to trigger RNAi in animals 30. Studies in transgenic plants that constitutively express the single-stranded PVX RNA also indicate that replication (during which dsRNA intermediates are formed), rather than mere accumulation of the viral genome, is required for RNA silencing activation 31.
Targets and mode of action of silencing suppressors
At present, little is known about the targets of viral-encoded silencing suppressors. Their modes of action have been largely inferred from overexpression experiments in different transgene-induced silencing systems, an approach that might have some limitations (Box 2). In principle, viral-encoded suppressors could affect – directly or indirectly – any step of the model depicted in Fig. 2. One could argue, however, that factors targeted against silencing components that are essential to the
An antiviral mechanism in animals?
Although, in animals, it is clear that RNA silencing plays a role in genome defence against transposable elements, there is still no evidence for it having an antiviral function. However, tools are available to address this important question. A recombinant Sindbis RNA virus (SIN) has been modified as a vector for endogenous gene overexpression in insects 58. Engineering this virus with exon fragments, rather than full-length cDNA, could help to elucidate whether VIGS operates in host organisms
Conclusion
Significant advances have been made in our understanding of the role and mechanism of RNA silencing over recent years. There is now strong evidence that RNA silencing operates as an innate antiviral defence in higher plants. Consistent with this finding, many plant viruses have elaborated proteins that suppress various steps of RNA silencing, a necessary adaptation if they are to replicate and spread in a plant. Forward genetic screens in Arabidopsis have revealed distinct genetic requirements
Acknowledgements
I thank all my colleagues at the Sainsbury Laboratory for fruitful discussions. I am particularly grateful to D. Baulcombe, A. Hamilton, T. Dalmay and J. Peart for critical reading of the manuscript. I acknowledge financial support from the European Union (Training and mobility of Researchers category 20, grant no. ERB4001GT9740039). Work in the Sainsbury Laboratory is supported by the Gatsby Charitable Foundation.
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