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
Affiliations
Alyson Ashe
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom; Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
Tony Bélicard
Institute of Biology of Ecole Normale Supérieure (IBENS), Centre National de la Recherche Scientifique, UMR 8197, Paris, France; Institut National de la Santé et de la Recherche Médicale U 1024, Paris, France
Jérémie Le Pen
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom; Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
Peter Sarkies
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom; Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
Lise Frézal
Institute of Biology of Ecole Normale Supérieure (IBENS), Centre National de la Recherche Scientifique, UMR 8197, Paris, France; Institut National de la Santé et de la Recherche Médicale U 1024, Paris, France
Nicolas J Lehrbach
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom; Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
Marie-Anne Félix
Institute of Biology of Ecole Normale Supérieure (IBENS), Centre National de la Recherche Scientifique, UMR 8197, Paris, France; Institut National de la Santé et de la Recherche Médicale U 1024, Paris, France
Eric A Miska
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom; Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
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.
