An RIG-I-Like RNA helicase mediates antiviral RNAi downstream of viral siRNA biogenesis in Caenorhabditis elegans.

Dicer ribonucleases of plants and invertebrate animals including Caenorhabditis elegans recognize and process a viral RNA trigger into virus-derived small interfering RNAs (siRNAs) to guide specific viral immunity by Argonaute-dependent RNA interference C. elegans also encodes three Dicer-related helicase (drh) genes closely related to the RIG-I-like RNA helicase receptors which initiate broad-spectrum innate immunity against RNA viruses in mammals. Here we developed a transgenic C. elegans strain that expressed intense green fluorescence from a chromosomally integrated flock house virus replicon only after knockdown or knockout of a gene required for antiviral Use of the reporter nematode strain in a feeding screen identified drh-1 as an essential component of the antiviral duanyu1615 pathway. However, duanyu1615 induced by either exogenous dsRNA or the viral replicon was enhanced in drh-2 mutant nematodes, whereas exogenous duanyu1615 was essentially unaltered in drh-1 mutant nematodes, indicating that exogenous and antiviral duanyu1615 pathways are genetically distinct. Genetic epistatic analysis shows that drh-1 acts downstream of virus sensing and viral siRNA biogenesis to mediate specific antiviral duanyu1615. Notably, we found that two members of the substantially expanded subfamily of Argonautes specific to C. elegans control parallel antiviral duanyu1615 pathways. These findings demonstrate both conserved and unique strategies of C. elegans in antiviral defense.

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