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A deletion polymorphism in the Caenorhabditis elegans RIG-I homolog disables viral RNA dicing and antiviral immunity.

Alyson Ashe | Tony Bélicard | Jérémie Le Pen | Peter Sarkies | Lise Frézal | Nicolas J Lehrbach | Marie-Anne Félix | Eric A Miska
eLife | 2013

RNA interference defends against viral infection in plant and animal cells. The nematode Caenorhabditis elegans and its natural pathogen, the positive-strand RNA virus Orsay, have recently emerged as a new animal model of host-virus interaction. Using a genome-wide association study in C. elegans wild populations and quantitative trait locus mapping, we identify a 159 base-pair deletion in the conserved drh-1 gene (encoding a RIG-I-like helicase) as a major determinant of viral sensitivity. We show that DRH-1 is required for the initiation of an antiviral RNAi pathway and the generation of virus-derived siRNAs (viRNAs). In mammals, RIG-I-domain containing proteins trigger an interferon-based innate immunity pathway in response to RNA virus infection. Our work in C. elegans demonstrates that the RIG-I domain has an ancient role in viral recognition. We propose that RIG-I acts as modular viral recognition factor that couples viral recognition to different effector pathways including RNAi and interferon responses. DOI:http://dx.doi.org/10.7554/eLife.00994.001.

Pubmed ID: 24137537

Research resources used in this publication

None found

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Associated grants

  • Agency: Wellcome Trust, United Kingdom
    Id: 092096
  • Agency: Cancer Research UK, United Kingdom
    Id: 11832
  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: Cancer Research UK, United Kingdom
    Id: RG57329

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Pfam (tool)

RRID:SCR_004726

A database of protein families, each represented by multiple sequence alignments and hidden Markov models (HMMs). Users can analyze protein sequences for Pfam matches, view Pfam family annotation and alignments, see groups of related families, look at the domain organization of a protein sequence, find the domains on a PDB structure, and query Pfam by keywords. There are two components to Pfam: Pfam-A and Pfam-B. Pfam-A entries are high quality, manually curated families that may automatically generate a supplement using the ADDA database. These automatically generated entries are called Pfam-B. Although of lower quality, Pfam-B families can be useful for identifying functionally conserved regions when no Pfam-A entries are found. Pfam also generates higher-level groupings of related families, known as clans (collections of Pfam-A entries which are related by similarity of sequence, structure or profile-HMM).

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RRID:SCR_004854

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RRID:SCR_006472

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