Journal article

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

Thomas J Hayman, Alan C Hsu, Tatiana B Kolesnik, Laura F Dagley, Joschka Willemsen, Michelle D Tate, Paul J Baker, Nadia J Kershaw, Lukasz Kedzierski, Andrew Webb, Peter A Wark, Katherine Kedzierska, Seth L Masters, Gabrielle T Belz, Marco Binder, Philip M Hansbro, Nicos A Nicola, Sandra E Nicholson



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..

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Awarded by National Health and Medical Research Council (NHMRC), Australia


Funding Acknowledgements

The authors thank Shannon Oliver and Carolina Alvarado from the Walter and Eliza Hall Institute of Medical Research for excellent animal husbandry. We thank Jane Murphy for assistance with genotyping and next-generation sequencing. This work was supported in part by the National Health and Medical Research Council (NHMRC), Australia (Project grants #1047248 and 1045762, Program grants #1016647 and 1113577), an NHMRC IRIISS grant 361646 and a Victorian State Government Operational Infrastructure Scheme grant. NAN and PMH are supported by NHMRC fellowships, MDT by an NHMRC Peter Doherty Career Development Fellowship, GTB by an NHMRC Senior Principal Research Fellowship, ACH by an AstraZeneca Research Fellowship and TJH by an Australian Postgraduate Award. None of the authors has a financial interest related to this work.