RRC ID 67760
Author Yamada T, Sato S, Sotoyama Y, Orba Y, Sawa H, Yamauchi H, Sasaki M, Takaoka A.
Title RIG-I triggers a signaling-abortive anti-SARS-CoV-2 defense in human lung cells.
Journal Nat Immunol
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.
Volume 22(7)
Pages 820-828
Published 2021-7-1
DOI 10.1038/s41590-021-00942-0
PII 10.1038/s41590-021-00942-0
PMID 33976430
MeSH A549 Cells Animals COVID-19 / immunology* Cell Line Cell Line, Tumor Chlorocebus aethiops DEAD Box Protein 58 / immunology* Dogs HEK293 Cells Humans Interferon Type I / immunology Interferons / immunology Lung / immunology* Lung / virology Madin Darby Canine Kidney Cells Pulmonary Disease, Chronic Obstructive / immunology RNA-Dependent RNA Polymerase / immunology Receptors, Immunologic / immunology* SARS-CoV-2 / immunology* Sf9 Cells Signal Transduction / immunology Vero Cells Viral Proteins / immunology
IF 20.479
Resource
DNA material CSII-CMV-MCS-IRES2-Bsd (RDB04385)