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PMID:24821782

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Citation

Sugimoto, N, Mitoma, H, Kim, T, Hanabuchi, S and Liu, YJ (2014) Helicase proteins DHX29 and RIG-I cosense cytosolic nucleic acids in the human airway system. Proc. Natl. Acad. Sci. U.S.A. 111:7747-52

Abstract

The recognition of cytoplasmic nucleic acid is critical for innate immune responses against microbial infection and is responsible for autoimmunity induced by dead cells. Here, we report the identification of a unique cytosolic nucleic acid cosensor in human airway epithelial cells and fibroblasts: DEAH (Asp-Glu-Ala-His) box polypeptide 29 (DHX29), a member of the DExD/H (Asp-Glu-x-Asp/His)-box helicase family. Knocking down DHX29 by siRNA attenuated the ability of cells to mount type I IFN and IL-6 in response to cytosolic nucleic acids and various viruses by blocking the activation of interferon regulatory factor 3 and NF-κB-p65. The cytosolic nucleic acid sensing by DHX29 in human epithelial cells and fibroblasts is independent of stimulator of interferon genes but is dependent on retinoic acid-inducible gene 1 (RIG-I) and mitochondrial antiviral signaling protein (MAVS). DHX29 binds directly to nucleic acids and interacts with RIG-I and MAVS through its helicase 1 domain, activating the RIG-I-MAVS-dependent cytosolic nucleic acid response. These results suggest that DHX29 is a cytosolic nucleic acid cosensor that triggers RIG-I/MAVS-dependent signaling pathways. This study will have important implications in drug and vaccine design for control of viral infections and viral-induced pathology in the airway.

Links

PubMed PMC4040624 Online version:10.1073/pnas.1400139111

Keywords

Cytosol/metabolism; DEAD Box Protein 58; DEAD-box RNA Helicases/metabolism; DNA, Complementary; Humans; Immunity, Innate/immunology; Nucleic Acids/genetics; Nucleic Acids/metabolism; Plasmids/genetics; RNA Helicases/metabolism; RNA Interference; Real-Time Polymerase Chain Reaction; Respiratory Mucosa/metabolism; Sequence Analysis, DNA; Virus Diseases/immunology; Viruses/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:DHX29

GO:0009615: detection of virus

ECO:0000315:

P

Fig. 2I, and J show that knockdown DHX29 expression shows a reduced production of immune response peptides IFN-β and IL-6 upon viral stimulation. The protein is referred to as DHX29 in the paper and is specifically mentioned to be human DHX29.

complete
CACAO 12280

Notes

See also

References

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