RIPLET and not TRIM25 is required for endogenous RIG-I-dependent anti-viral responses
Publication Year 2019-10,Volume 97,Issue #9,Page 840-852
Journal Title
Immunology and Cell Biology
Publication Type
Journal Article
The innate immune system is our first line of defence against viral pathogens. Host cell pattern recognition receptors (PRRs) sense viral components and initiate immune signalling cascades that result in the production of an array of cytokines to combat infection. The retinoic acid inducible gene-I (RIG-I) is a PRR that recognises viral RNA and, when activated, results in the production of type I and III interferons (IFNs) and the up-regulation of IFN-stimulated genes. Ubiquitination of RIG-I by the E3 ligases TRIM25 and Riplet is thought to be requisite for RIG-I activation; however, recent studies have questioned the relative importance of these two enzymes for RIG-I signalling. Here we show that deletion of Trim25 does not affect the IFN response to either influenza A virus (IAV), influenza B virus, Sendai virus, or to several RIG-I agonists. This is in contrast to deletion of either Rig-i or Riplet, which completely abrogated RIG-I-IFN responses. This was consistent in both mouse and human cell lines, as well as normal human bronchial cells. With most of the current TRIM25 literature based on exogenous expression, these findings provide critical evidence that Riplet, and not TRIM25, is required endogenously for the ubiquitination of RIG-I. Despite this, loss of TRIM25 results in greater susceptibility to IAV infection in vivo suggesting that it may have an alternative role in host anti-viral defence. This study refines our understanding of RIG-I signaling in viral infections and will inform future studies in the field. This article is protected by copyright. All rights reserved.
WEHI Research Division(s)
Population Health And Immunity; Inflammation; Advanced Technology And Biology; Personalised Oncology
PubMed ID
NHMRC Grants
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Creation Date: 2019-07-26 09:44:14
Last Modified: 2019-10-28 11:31:31
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