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.2021 Jul;22(7):820-828.
doi: 10.1038/s41590-021-00942-0. Epub 2021 May 11.

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

Taisho Yamada 1 2, Seiichi Sato 1 2, Yuki Sotoyama 1 2, Yasuko Orba 3 4, Hirofumi Sawa 3 4 5, Hajime Yamauchi 1, Michihito Sasaki 3, Akinori Takaoka 6 7
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RIG-I triggers a signaling-abortive anti-SARS-CoV-2 defense in human lung cells

Taisho Yamada et al. Nat Immunol. 2021 Jul.
Free article

Abstract

Efficient immune responses against viral infection are determined by sufficient activation of nucleic acid sensor-mediated innate immunity1,2. 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.

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References

    1. Takaoka, A. & Yamada, T. Regulation of signaling mediated by nucleic acid sensors for innate interferon-mediated responses during viral infection. Int. Immunol. 31, 477–488 (2019).-PubMed-DOI
    1. Goubau, D., Deddouche, S. & Reis e Sousa, C. Cytosolic sensing of viruses. Immunity 38, 855–869 (2013).-PubMed-PMC-DOI
    1. Gandhi, R. T., Lynch, J. B. & del Rio, C. Mild or moderate COVID-19. N. Engl. J. Med. 383, 1757–1766 (2020).-PubMed-DOI
    1. Sanchez-Ramirez, D. C. & Mackey, D. Underlying respiratory diseases, specifically COPD, and smoking are associated with severe COVID-19 outcomes: a systematic review and meta-analysis. Respir. Med. 171, 106096 (2020).-PubMed-PMC-DOI
    1. Zhao, Q. et al. The impact of COPD and smoking history on the severity of COVID-19: a systemic review and meta-analysis. J. Med. Virol. 92, 1915–1921 (2020).

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