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Title: Caenorhabditis elegans RIG-I-like receptor DRH-1 signals via CARDs to activate antiviral immunity in intestinal cells
Upon sensing viral RNA, mammalian RIG-I-like receptors (RLRs) activate downstream signals using caspase activation and recruitment domains (CARDs), which ultimately promote transcriptional immune responses that have been well studied. In contrast, the downstream signaling mechanisms for invertebrate RLRs are much less clear. For example, theCaenorhabditis elegansRLR DRH-1 lacks annotated CARDs and up-regulates the distinct output of RNA interference. Here, we found that similar to mammal RLRs, DRH-1 signals through two tandem CARDs (2CARD) to induce a transcriptional immune response. Expression of DRH-1(2CARD) alone in the intestine was sufficient to induce immune gene expression, increase viral resistance, and promote thermotolerance, a phenotype previously associated with immune activation inC. elegans. We also found that DRH-1 is required in the intestine to induce immune gene expression, and we demonstrate subcellular colocalization of DRH-1 puncta with double-stranded RNA inside the cytoplasm of intestinal cells upon viral infection. Altogether, our results reveal mechanistic and spatial insights into antiviral signaling inC. elegans, highlighting unexpected parallels in RLR signaling betweenC. elegansand mammals.  more » « less
Award ID(s):
2301657
PAR ID:
10557718
Author(s) / Creator(s):
; ;
Publisher / Repository:
PNAS
Date Published:
Journal Name:
Proceedings of the National Academy of Sciences
Volume:
121
Issue:
29
ISSN:
0027-8424
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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