| 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 Lambda
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) |
