Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses
| Autor: | Thiagarajan Venkataraman, Rachel Elsby, Glen N. Barber, Shinobu Saijo, Gisela Caceres, Yoichiro Iwakura, Maikel Valdes, Shigeru Kakuta |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Interferon-Induced Helicase IFIH1 Immunology Mice Transgenic Nerve Tissue Proteins Receptors Cell Surface Biology Virus Vesicular stomatitis Indiana virus DEAD-box RNA Helicases Mice Rhabdoviridae Infections Cardiovirus Infections Immunology and Allergy Animals Encephalomyocarditis virus DEAD Box Protein 58 Cells Cultured LGP2 RNA Membrane Proteins MDA5 biology.organism_classification Virology RNA Helicase A Immunity Innate Helicase Gene Cell biology Mice Inbred C57BL Vesicular stomatitis virus Female Signal Transduction |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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