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RIG-I triggers a signaling-abortive anti-SARS-CoV-2 defense in human lung cells
Title: | RIG-I triggers a signaling-abortive anti-SARS-CoV-2 defense in human lung cells |
Authors: | Yamada, Taisho Browse this author →KAKEN DB | Sato, Seiichi Browse this author | Sotoyama, Yuki Browse this author | Orba, Yasuko Browse this author | Sawa, Hirofumi Browse this author | Yamauchi, Hajime Browse this author | Sasaki, Michihito Browse this author | Takaoka, Akinori Browse this author →KAKEN DB |
Issue Date: | Jul-2021 |
Publisher: | Nature Research |
Journal Title: | Nature immunology |
Volume: | 22 |
Issue: | 7 |
Start Page: | 820 |
End Page: | 828 |
Publisher DOI: | 10.1038/s41590-021-00942-0 |
Abstract: | Efficient immune responses against viral infection are determined by sufficient activation of nucleic acid sensor-mediated innate immunity(1,2). Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains an ongoing global pandemic. It is an urgent challenge to clarify the innate recognition mechanism to control this virus. Here we show that retinoic acid-inducible gene-I (RIG-I) sufficiently restrains SARS-CoV-2 replication in human lung cells in a type I/III interferon (IFN)-independent manner. RIG-I recognizes the 3 ' untranslated region of the SARS-CoV-2 RNA genome via the helicase domains, but not the C-terminal domain. This new mode of RIG-I recognition does not stimulate its ATPase, thereby aborting the activation of the conventional mitochondrial antiviral-signaling protein-dependent pathways, which is in accordance with lack of cytokine induction. Nevertheless, the interaction of RIG-I with the viral genome directly abrogates viral RNA-dependent RNA polymerase mediation of the first step of replication. Consistently, genetic ablation of RIG-I allows lung cells to produce viral particles that expressed the viral spike protein. By contrast, the anti-SARS-CoV-2 activity was restored by all-trans retinoic acid treatment through upregulation of RIG-I protein expression in primary lung cells derived from patients with chronic obstructive pulmonary disease. Thus, our findings demonstrate the distinctive role of RIG-I as a restraining factor in the early phase of SARS-CoV-2 infection in human lung cells. |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/83792 |
Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 高岡 晃教
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