title: A deletion polymorphism in the Caenorhabditis elegans RIG-I homolog disables viral RNA dicing and antiviral immunity.
abstract: 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.
authors.affiliation: Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge , Cambridge , United Kingdom ; Department of Biochemistry , University of Cambridge , Cambridge , United Kingdom.
authors.forename: Alyson
authors.initials: A
authors.lastname: Ashe
authors.forename: Tony
authors.initials: T
authors.lastname: Bélicard
authors.forename: Jérémie
authors.initials: J
authors.lastname: Le Pen
authors.forename: Peter
authors.initials: P
authors.lastname: Sarkies
authors.forename: Lise
authors.initials: L
authors.lastname: Frézal
authors.forename: Nicolas J
authors.initials: NJ
authors.lastname: Lehrbach
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Félix
authors.forename: Eric A
authors.initials: EA
authors.lastname: Miska
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000276:immunology / Q000821:virology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D017353:Gene Deletion; D010942:Plant Viruses / Q000235:genetics / Q000502:physiology*; D011110:Polymorphism, Genetic; D040641:Quantitative Trait Loci; D012367:RNA, Viral / Q000235:genetics*
chemical_list: D029742:Caenorhabditis elegans Proteins; D012367:RNA, Viral
keywords: C. elegans; RNA interference; immunity; virus infection