SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

LGP2 plays a critical role in sensitizing mda-5 to activation by double-stranded RNA.

Childs, KS; Randall, RE; Goodbourn, S (2013) LGP2 plays a critical role in sensitizing mda-5 to activation by double-stranded RNA. PLOS ONE, 8 (5). e64202. ISSN 1932-6203 https://doi.org/10.1371/journal.pone.0064202
SGUL Authors: Childs, Kay Samantha Goodbourn, Stephen Edward

[img]
Preview
["document_typename_application/pdf; charset=binary" not defined] Published Version
Download (1MB) | Preview

Abstract

The 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.

Item Type: Article
Additional Information: ©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.
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: PLOS ONE
ISSN: 1932-6203
Dates:
DateEvent
9 May 2013Published
PubMed ID: 23671710
Web of Science ID: 23671710
Download EPMC Full text (PDF)
Download EPMC Full text (HTML)
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/101148
Publisher's version: https://doi.org/10.1371/journal.pone.0064202

Actions (login required)

Edit Item Edit Item