2024-03-29T09:07:16Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/595962022-11-17T02:08:08Zhdl_2115_20076hdl_2115_597DDX60 Is Involved in RIG-I-Dependent and Independent Antiviral Responses, and Its Function Is Attenuated by Virus-Induced EGFR ActivationOshiumi, HiroyukiMiyashita, MoekoOkamoto, MasaakiMorioka, YukaOkabe, MasaruMatsumoto, MisakoSeya, Tsukasa491RIG-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.Cell PressJournal Articleapplication/pdfhttp://hdl.handle.net/2115/59596https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/59596/1/Cell%20reports11-8p.1193-1207.pdf2211-1247Cell reports118119312072015-05-26enginfo:pmid/25981042info:doi/10.1016/j.celrep.2015.04.047http://creativecommons.org/licenses/by-nc-nd/4.0/publisher