RIPLET, and not TRIM25, is required for endogenous RIG-I-dependent antiviral responses

Hayman, TJ; Hsu, AC; Kolesnik, TB; Dagley, LF; Willemsen, J; Tate, MD; Baker, PJ; Kershaw, NJ; Kedzierski, L; Webb, AI; Wark, PA; Kedzierska, K; Masters, SL; Belz, GT; Binder, M; Hansbro, PM; Nicola, NA; Nicholson, SE

RIPLET, and not TRIM25, is required for endogenous RIG-I-dependent antiviral responses

Hayman, TJ Hsu, AC Kolesnik, TB Dagley, LF Willemsen, J Tate, MD Baker, PJ Kershaw, NJ Kedzierski, L Webb, AI Wark, PA Kedzierska, K Masters, SL Belz, GT Binder, M Hansbro, PM

Nicola, NA Nicholson, SE

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Publication Type:: Journal Article
Citation:: Immunology and Cell Biology, 2019, 97 (9), pp. 840 - 852
Issue Date:: 2019-10-01

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Field	Value	Language
dc.contributor.author	Hayman, TJ	en_US
dc.contributor.author	Hsu, AC	en_US
dc.contributor.author	Kolesnik, TB	en_US
dc.contributor.author	Dagley, LF	en_US
dc.contributor.author	Willemsen, J	en_US
dc.contributor.author	Tate, MD	en_US
dc.contributor.author	Baker, PJ	en_US
dc.contributor.author	Kershaw, NJ	en_US
dc.contributor.author	Kedzierski, L	en_US
dc.contributor.author	Webb, AI	en_US
dc.contributor.author	Wark, PA	en_US
dc.contributor.author	Kedzierska, K	en_US
dc.contributor.author	Masters, SL	en_US
dc.contributor.author	Belz, GT	en_US
dc.contributor.author	Binder, M	en_US
dc.contributor.author	Hansbro, PM https://orcid.org/0000-0002-4741-3035	en_US
dc.contributor.author	Nicola, NA	en_US
dc.contributor.author	Nicholson, SE	en_US
dc.date.available	2019-07-12	en_US
dc.date.issued	2019-10-01	en_US
dc.identifier.citation	Immunology and Cell Biology, 2019, 97 (9), pp. 840 - 852	en_US
dc.identifier.issn	0818-9641	en_US
dc.identifier.uri	http://hdl.handle.net/10453/136494
dc.description.abstract	© 2019 Australian and New Zealand Society for Immunology Inc. The innate immune system is our first line of defense against viral pathogens. Host cell pattern recognition receptors sense viral components and initiate immune signaling cascades that result in the production of an array of cytokines to combat infection. Retinoic acid–inducible gene-I (RIG-I) is a pattern recognition receptor that recognizes viral RNA and, when activated, results in the production of type I and III interferons (IFNs) and the upregulation of IFN-stimulated genes. Ubiquitination of RIG-I by the E3 ligases tripartite motif-containing 25 (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 signaling. In this study, we show that deletion of Trim25 does not affect the IFN response to either influenza A virus (IAV), influenza B virus, Sendai virus or several RIG-I agonists. This is in contrast to deletion of either Rig-i or Riplet, which completely abrogated RIG-I-dependent IFN responses. This was consistent in both mouse and human cell lines, as well as in 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 antiviral defense. This study refines our understanding of RIG-I signaling in viral infections and will inform future studies in the field.	en_US
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT1079187
dc.relation.ispartof	Immunology and Cell Biology	en_US
dc.relation.isbasedon	10.1111/imcb.12284	en_US
dc.subject.classification	Immunology	en_US
dc.subject.mesh	Cell Line	en_US
dc.subject.mesh	Epithelial Cells	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred C57BL	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Ubiquitin-Protein Ligases	en_US
dc.subject.mesh	DNA-Binding Proteins	en_US
dc.subject.mesh	Transcription Factors	en_US
dc.subject.mesh	RNA	en_US
dc.subject.mesh	Antiviral Agents	en_US
dc.subject.mesh	Ligands	en_US
dc.subject.mesh	Signal Transduction	en_US
dc.subject.mesh	Gene Deletion	en_US
dc.subject.mesh	Tripartite Motif Proteins	en_US
dc.subject.mesh	DEAD Box Protein 58	en_US
dc.subject.mesh	A549 Cells	en_US
dc.title	RIPLET, and not TRIM25, is required for endogenous RIG-I-dependent antiviral responses	en_US
dc.type	Journal Article
utslib.citation.volume	9	en_US
utslib.citation.volume	97	en_US
utslib.for	1107 Immunology	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	9	en_US
pubs.publication-status	Published	en_US
pubs.volume	97	en_US

Abstract:

© 2019 Australian and New Zealand Society for Immunology Inc. The innate immune system is our first line of defense against viral pathogens. Host cell pattern recognition receptors sense viral components and initiate immune signaling cascades that result in the production of an array of cytokines to combat infection. Retinoic acid–inducible gene-I (RIG-I) is a pattern recognition receptor that recognizes viral RNA and, when activated, results in the production of type I and III interferons (IFNs) and the upregulation of IFN-stimulated genes. Ubiquitination of RIG-I by the E3 ligases tripartite motif-containing 25 (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 signaling. In this study, we show that deletion of Trim25 does not affect the IFN response to either influenza A virus (IAV), influenza B virus, Sendai virus or several RIG-I agonists. This is in contrast to deletion of either Rig-i or Riplet, which completely abrogated RIG-I-dependent IFN responses. This was consistent in both mouse and human cell lines, as well as in 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 antiviral defense. This study refines our understanding of RIG-I signaling in viral infections and will inform future studies in the field.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/136494