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

Nature. 2005 Aug 18;436(7053):1040-1043. doi: 10.1038/nature03870.


The worm Caenorhabditis elegans is a model system for studying many aspects of biology, including host responses to bacterial pathogens, 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 cooperatively. 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 plants and insects. 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 protein 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 inhibitor 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Antiviral Agents
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / virology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Disease Models, Animal
  • Gene Expression Regulation, Viral*
  • Herpesviridae / genetics*
  • Herpesviridae / growth & development*
  • Host-Parasite Interactions
  • RNA Interference*
  • RNA, Double-Stranded / genetics
  • RNA, Double-Stranded / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Ribonuclease III / metabolism
  • Transgenes
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Virus Replication / genetics*


  • Antiviral Agents
  • Caenorhabditis elegans Proteins
  • RNA, Double-Stranded
  • RNA, Small Interfering
  • Viral Proteins
  • rde-1 protein, C elegans
  • Ribonuclease III