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RIG-I triggers a signaling-abortive anti-SARS-CoV-2 defense in human lung cells

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/83792

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)

Submitter: 高岡 晃教

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