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dc.contributor.authorChilds, Kay S.
dc.contributor.authorRandall, Richard E.
dc.contributor.authorGoodbourn, Stephen
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 .
dc.identifier.otherORCID: /0000-0002-9304-6678/work/60427018
dc.descriptionThis work was supported by The Wellcome Trust (Grant Numbers AL087751/B to SG and 087751/A/08/Z to RER). (
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.relation.ispartofPLoS Oneen
dc.subjectParamyxovirus v-proteinsen
dc.subjectInducible gene-Ien
dc.subjectInnate immune sensoren
dc.subjectIfn-beta promoteren
dc.subjectAntiviral responsesen
dc.subjectHilicase LGP2en
dc.subjectQH426 Geneticsen
dc.titleLGP2 plays a critical role in sensitizing mda-5 to activation by double-stranded RNAen
dc.typeJournal articleen
dc.contributor.sponsorThe Wellcome Trusten
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.description.statusPeer revieweden

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