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dc.contributor.authorChilds, Kay S.
dc.contributor.authorRandall, Richard E.
dc.contributor.authorGoodbourn, Stephen
dc.date.accessioned2014-07-16T14:31:04Z
dc.date.available2014-07-16T14:31:04Z
dc.date.issued2013-05-09
dc.identifier.citationChilds , K S , Randall , R E & Goodbourn , S 2013 , ' LGP2 plays a critical role in sensitizing mda-5 to activation by double-stranded RNA ' , PLoS One , vol. 8 , no. 5 , e64202 . https://doi.org/10.1371/journal.pone.0064202en
dc.identifier.issn1932-6203
dc.identifier.otherPURE: 131399379
dc.identifier.otherPURE UUID: 3797b1ab-4d08-4480-a3d2-aaf344670f32
dc.identifier.otherWOS: 000319737700068
dc.identifier.otherScopus: 84877326407
dc.identifier.otherORCID: /0000-0002-9304-6678/work/60427018
dc.identifier.urihttp://hdl.handle.net/10023/5028
dc.descriptionThis work was supported by The Wellcome Trust (Grant Numbers AL087751/B to SG and 087751/A/08/Z to RER). (http://www.wellcome.ac.uk/).en
dc.description.abstractThe DExD/H box RNA helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation associated gene-5 (mda-5) sense viral RNA in the cytoplasm of infected cells and activate signal transduction pathways that trigger the production of type I interferons (IFNs). Laboratory of genetics and physiology 2 (LGP2) is thought to influence IFN production by regulating the activity of RIG-I and mda-5, although its mechanism of action is not known and its function is controversial. Here we show that expression of LGP2 potentiates IFN induction by polyinosinic-polycytidylic acid [poly(I:C)], commonly used as a synthetic mimic of viral dsRNA, and that this is particularly significant at limited levels of the inducer. The observed enhancement is mediated through co-operation with mda-5, which depends upon LGP2 for maximal activation in response to poly(I:C). This co-operation is dependent upon dsRNA binding by LGP2, and the presence of helicase domain IV, both of which are required for LGP2 to interact with mda-5. In contrast, although RIG-I can also be activated by poly(I:C), LGP2 does not have the ability to enhance IFN induction by RIG-I, and instead acts as an inhibitor of RIG-I-dependent poly(I:C) signaling. Thus the level of LGP2 expression is a critical factor in determining the cellular sensitivity to induction by dsRNA, and this may be important for rapid activation of the IFN response at early times post-infection when the levels of inducer are low.
dc.format.extent8
dc.language.isoeng
dc.relation.ispartofPLoS Oneen
dc.rightsCopyright: © 2013 Childs et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. http://creativecommons.org/licenses/by/3.0/en
dc.subjectParamyxovirus v-proteinsen
dc.subjectInducible gene-Ien
dc.subjectInnate immune sensoren
dc.subjectIfn-beta promoteren
dc.subjectRIG-Ien
dc.subjectAntiviral responsesen
dc.subjectHilicase LGP2en
dc.subjectSignal-transductionen
dc.subjectInterferon-betaen
dc.subjectRecognitionen
dc.subjectQH426 Geneticsen
dc.subject.lccQH426en
dc.titleLGP2 plays a critical role in sensitizing mda-5 to activation by double-stranded RNAen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0064202
dc.description.statusPeer revieweden


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