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Animal virus replication and RNAi-mediated antiviral silencing in Caenorhabditis elegans

Abstract

The worm Caenorhabditis elegans is a model system for studying many aspects of biology, including host responses to bacterial pathogens1,2, but it is not known to support replication of any virus. Plants and insects encode multiple Dicer enzymes that recognize distinct precursors of small RNAs and may act cooperatively3,4,5,6,7. However, it is not known whether the single Dicer of worms and mammals is able to initiate the small RNA-guided RNA interference (RNAi) antiviral immunity as occurs in plants8 and insects9. Here we show complete replication of the Flock house virus (FHV) bipartite, plus-strand RNA genome in C. elegans. We show that FHV replication in C. elegans triggers potent antiviral silencing that requires RDE-1, an Argonaute protein10,11 essential for RNAi mediated by small interfering RNAs (siRNAs) but not by microRNAs. This immunity system is capable of rapid virus clearance in the absence of FHV B2 protein, which acts as a broad-spectrum RNAi inhibitor9,12 upstream of rde-1 by targeting the siRNA precursor. This work establishes a C. elegans model for genetic studies of animal virus–host interactions and indicates that mammals might use a siRNA pathway as an antiviral response.

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Figure 1: Replication and silencing of FHV in C. elegans.
Figure 2: FHV RNAi suppressor is active in rde-1 worms.
Figure 3: FHV B2 is a dsRNA-binding protein and inhibits siRNA production in vitro.

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Acknowledgements

We thank X. Huang for recommending the use of pPD49.83, and the Caenorhabditis Genetics Center funded by the National Center for Research Resources of the National Institutes of Health for some of the strains used in this work. This project was supported by an NIH grant and USDA National Research Initiative Competitive Grants Program awards (to S.W.D.) and UC Riverside startup funds (to M.M).

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Correspondence to S. W. Ding.

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Lu, R., Maduro, M., Li, F. et al. Animal virus replication and RNAi-mediated antiviral silencing in Caenorhabditis elegans. Nature 436, 1040–1043 (2005). https://doi.org/10.1038/nature03870

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