DDX60 Is Involved in RIG-I-Dependent and Independent Antiviral Responses, and Its Function Is Attenuated by Virus-Induced EGFR Activation

• Oshiumi, Hiroyuki

• Miyashita, Moeko

• Okamoto, Masaaki

• Morioka, Yuka

• Okabe, Masaru

• Matsumoto, Misako

• Seya, Tsukasa

抄録

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.

収録刊行物

• Cell reports

  Cell reports 11 (8), 1193-1207, 2015-05-26

  Cell Press

キーワード

• General Biochemistry, Genetics and Molecular Biology

詳細情報

• CRID: 1050564288971667072
• NII論文ID: 120005625293
• DOI: 10.1016/j.celrep.2015.04.047
• HANDLE: 2115/59596
• ISSN: 22111247
• Web Site: https://api.elsevier.com/content/article/PII:S2211124715004647?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S2211124715004647?httpAccept=text/plain
• 本文言語コード: en
• 資料種別: journal article
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