Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses

Thiagarajan Venkataraman, Maikel Valdes, Rachel Elsby, Shigeru Kakuta, Gisela Caceres, Shinobu Saijo, Yoichiro Iwakura, Glen N. Barber

Research output: Contribution to journalArticle

286 Scopus citations

Abstract

The DExD/H box RNA helicase retinoic acid-inducible gene I (RIG-I) and the melanoma differentiation-associated gene 5 (MDA5) are key intracellular receptors that recognize virus infection to produce type I IFN. A third helicase gene, Lgp2, is homologous to Rig-I and Mda5 but lacks a caspase activation and recruitment domain. We generated Lgp2 -deficient mice and report that the loss of this gene greatly sensitizes cells to cytosolic polyinosinic/polycytidylic acid-mediated induction of type I IFN. However, negative feedback inhibition of IFN-β transcription was found to be normal in the absence of LGP2, indicating that LGP2 is not the primary negative regulator of type I IFN production. Our data further indicate that Lgp2-/- mice exhibited resistance to lethal vesicular stomatitis virus infection, a virus whose replicative RNA intermediates are recognized specifically by RIG-I rather than by MDA5 to trigger the production of type I IFN. However, mice lacking LGP2 were observed to exhibit a defect in type I IFN production in response to infection by the encephalomyocarditis virus, the replication of which activates MDA5-dependent innate immune responses. Collectively, our data indicate a disparate regulatory role for LGP2 in the triggering of innate immune signaling pathways following RNA virus infection.

Original languageEnglish (US)
Pages (from-to)6444-6455
Number of pages12
JournalJournal of Immunology
Volume178
Issue number10
DOIs
StatePublished - May 15 2007

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Venkataraman, T., Valdes, M., Elsby, R., Kakuta, S., Caceres, G., Saijo, S., Iwakura, Y., & Barber, G. N. (2007). Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses. Journal of Immunology, 178(10), 6444-6455. https://doi.org/10.4049/jimmunol.178.10.6444