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

276 Citations (Scopus)

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

Fingerprint

RNA Helicases
Antiviral Agents
Genes
Melanoma
Virus Diseases
Tretinoin
RNA Virus Infections
Encephalomyocarditis virus
Poly I-C
Vesicular Stomatitis
Virus Replication
Innate Immunity
RNA
Viruses
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Venkataraman, T., Valdes, M., Elsby, R., Kakuta, S., Caceres, G., Saijo, S., ... Barber, G. N. (2007). Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses. Journal of Immunology, 178(10), 6444-6455.

Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses. / Venkataraman, Thiagarajan; Valdes, Maikel; Elsby, Rachel; Kakuta, Shigeru; Caceres, Gisela; Saijo, Shinobu; Iwakura, Yoichiro; Barber, Glen N.

In: Journal of Immunology, Vol. 178, No. 10, 15.05.2007, p. 6444-6455.

Research output: Contribution to journalArticle

Venkataraman, T, Valdes, M, Elsby, R, Kakuta, S, Caceres, G, Saijo, S, Iwakura, Y & Barber, GN 2007, 'Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses', Journal of Immunology, vol. 178, no. 10, pp. 6444-6455.
Venkataraman T, Valdes M, Elsby R, Kakuta S, Caceres G, Saijo S et al. Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses. Journal of Immunology. 2007 May 15;178(10):6444-6455.
Venkataraman, Thiagarajan ; Valdes, Maikel ; Elsby, Rachel ; Kakuta, Shigeru ; Caceres, Gisela ; Saijo, Shinobu ; Iwakura, Yoichiro ; Barber, Glen N. / Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses. In: Journal of Immunology. 2007 ; Vol. 178, No. 10. pp. 6444-6455.
@article{83ce45868a9d493f83032a59be512b15,
title = "Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses",
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.",
author = "Thiagarajan Venkataraman and Maikel Valdes and Rachel Elsby and Shigeru Kakuta and Gisela Caceres and Shinobu Saijo and Yoichiro Iwakura and Barber, {Glen N}",
year = "2007",
month = "5",
day = "15",
language = "English",
volume = "178",
pages = "6444--6455",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "10",

}

TY - JOUR

T1 - Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses

AU - Venkataraman, Thiagarajan

AU - Valdes, Maikel

AU - Elsby, Rachel

AU - Kakuta, Shigeru

AU - Caceres, Gisela

AU - Saijo, Shinobu

AU - Iwakura, Yoichiro

AU - Barber, Glen N

PY - 2007/5/15

Y1 - 2007/5/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34248168157&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34248168157&partnerID=8YFLogxK

M3 - Article

VL - 178

SP - 6444

EP - 6455

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 10

ER -