Cell Reports
Volume 11, Issue 8, 26 May 2015, Pages 1193-1207
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Article
DDX60 Is Involved in RIG-I-Dependent and Independent Antiviral Responses, and Its Function Is Attenuated by Virus-Induced EGFR Activation

https://doi.org/10.1016/j.celrep.2015.04.047Get rights and content
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open access

Highlights

  • Human DDX60 functions as a ligand-specific sentinel for RIG-I activation

  • DDX60 plays a role in RIG-I-mediated innate immune response in vivo

  • DDX60 is involved in a viral RNA degradation pathway

  • Virus-mediated EGF receptor activation attenuates DDX60 antiviral activities

Summary

RIG-I-mediated type I interferon (IFN) production and nuclease-mediated viral RNA degradation are essential for antiviral innate immune responses. DDX60 is an IFN-inducible cytoplasmic helicase. Here, we report that DDX60 is a sentinel for both RIG-I activation and viral RNA degradation. We show that DDX60 is an upstream factor of RIG-I that activates RIG-I signaling in a ligand-specific manner. DDX60 knockout attenuates RIG-I signaling and significantly reduces virus-induced type I IFN production in vivo. In addition, we show that DDX60 is involved in RIG-I-independent viral RNA degradation. DDX60 and RIG-I adaptor MAVS double-knockout mice reveal a role for DDX60-dependent RNA degradation in antiviral responses. Several viruses induced DDX60 phosphorylation via epidermal growth factor receptor (EGFR), leading to attenuation of the DDX60 antiviral activities. Our results define DDX60 as a sentinel for cytoplasmic antiviral response, which is counteracted by virus-mediated EGF receptor activation.

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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Co-first author

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Present address: Laboratory for Biologics Development, Research Center for Zoonosis Control, Hokkaido University, Sapporo 060-8638, Japan