RNA interference is an antiviral defence mechanism in Caenorhabditis elegans

Abstract

RNA interference (RNAi) is an evolutionarily conserved sequence-specific post-transcriptional gene silencing mechanism that is well defined genetically in Caenorhabditis elegans1,2,3,4. RNAi has been postulated to function as an adaptive antiviral immune mechanism in the worm, but there is no experimental evidence for this. Part of the limitation is that there are no known natural viral pathogens of C. elegans. Here we describe an infection model in C. elegans using the mammalian pathogen vesicular stomatitis virus (VSV) to study the role of RNAi in antiviral immunity. VSV infection is potentiated in cells derived from RNAi-defective worm mutants (rde-1; rde-4), leading to the production of infectious progeny virus, and is inhibited in mutants with an enhanced RNAi response (rrf-3; eri-1). Because the RNAi response occurs in the absence of exogenously added VSV small interfering RNAs, these results show that RNAi is activated during VSV infection and that RNAi is a genuine antiviral immune defence mechanism in the worm.

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Figure 1: VSV infection of C. elegans cells in culture.
Figure 2: Increased infection of RNAi-deficient mutants.
Figure 3: Increased resistance of RNAi-hypersensitive mutants to VSV infection.
Figure 4: Virus-specific siRNAs in infected N2 cells.

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Acknowledgements

We thank the Caenorhabditis Genetics Center for most of the strains used in this study; M. Kaufmann for suggestions; and K. Mitchell for technical assistance in the initial phases of this study. This work was funded in part by UAMS Foundation research funds (M.C.), from the BRIN Program of the National Center for Research Resources (S.C.M. and M.C.), and startup funds (K.M.).

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Correspondence to Marie Chow or Khaled Machaca.

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M.A.W. is also employed at, and has financial interests in, Gtx. Inc., which holds an exclusive licence for recombinant VSV technology from the University of Tennessee Research Foundation.

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Wilkins, C., Dishongh, R., Moore, S. et al. RNA interference is an antiviral defence mechanism in Caenorhabditis elegans. Nature 436, 1044–1047 (2005). https://doi.org/10.1038/nature03957

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