The Caenorhabditis elegans RIG-I Homolog DRH-1 Mediates the Intracellular Pathogen Response upon Viral Infection. J Virol 2020 Jan 06;94(2)
Date
10/18/2019Pubmed ID
31619561Pubmed Central ID
PMC6955277DOI
10.1128/JVI.01173-19Scopus ID
2-s2.0-85077667459 (requires institutional sign-in at Scopus site) 37 CitationsAbstract
Mammalian retinoic acid-inducible gene I (RIG-I)-like receptors detect viral double-stranded RNA (dsRNA) and 5'-triphosphorylated RNA to activate the transcription of interferon genes and promote antiviral defense. The Caenorhabditis elegans RIG-I-like receptor DRH-1 promotes defense through antiviral RNA interference (RNAi), but less is known about its role in regulating transcription. Here, we describe a role for DRH-1 in directing a transcriptional response in C. elegans called the intracellular pathogen response (IPR), which is associated with increased pathogen resistance. The IPR includes a set of genes induced by diverse stimuli, including intracellular infection and proteotoxic stress. Previous work suggested that the proteotoxic stress caused by intracellular infections might be the common trigger of the IPR, but here, we demonstrate that different stimuli act through distinct pathways. Specifically, we demonstrate that DRH-1/RIG-I is required for inducing the IPR in response to Orsay virus infection but not in response to other triggers like microsporidian infection or proteotoxic stress. Furthermore, DRH-1 appears to be acting independently of its known role in RNAi. Interestingly, expression of the replication-competent Orsay virus RNA1 segment alone is sufficient to induce most of the IPR genes in a manner dependent on RNA-dependent RNA polymerase activity and on DRH-1. Altogether, these results suggest that DRH-1 is a pattern recognition receptor that detects viral replication products to activate the IPR stress/immune program in C. elegansIMPORTANCEC. elegans lacks homologs of most mammalian pattern recognition receptors, and how nematodes detect pathogens is poorly understood. We show that the C. elegans RIG-I homolog DRH-1 mediates the induction of the intracellular pathogen response (IPR), a novel transcriptional defense program, in response to infection by the natural C. elegans viral pathogen Orsay virus. DRH-1 appears to act as a pattern recognition receptor to induce the IPR transcriptional defense program by sensing the products of viral RNA-dependent RNA polymerase activity. Interestingly, this signaling role of DRH-1 is separable from its previously known role in antiviral RNAi. In addition, we show that there are multiple host pathways for inducing the IPR, shedding light on the regulation of this novel transcriptional immune response.
Author List
Sowa JN, Jiang H, Somasundaram L, Tecle E, Xu G, Wang D, Troemel ERAuthor
Eillen Tecle PhD Assistant Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCaenorhabditis elegans
Caenorhabditis elegans Proteins
DEAD-box RNA Helicases
Host-Parasite Interactions
Nodaviridae
RNA Virus Infections
Receptors, Pattern Recognition
