| RRC ID |
68941
|
| 著者 |
Yoo JS, Sasaki M, Cho SX, Kasuga Y, Zhu B, Ouda R, Orba Y, de Figueiredo P, Sawa H, Kobayashi KS.
|
| タイトル |
SARS-CoV-2 inhibits induction of the MHC class I pathway by targeting the STAT1-IRF1-NLRC5 axis.
|
| ジャーナル |
Nat Commun
|
| Abstract |
The MHC class I-mediated antigen presentation pathway plays a critical role in antiviral immunity. Here we show that the MHC class I pathway is targeted by SARS-CoV-2. Analysis of the gene expression profile from COVID-19 patients as well as SARS-CoV-2 infected epithelial cell lines reveals that the induction of the MHC class I pathway is inhibited by SARS-CoV-2 infection. We show that NLRC5, an MHC class I transactivator, is suppressed both transcriptionally and functionally by the SARS-CoV-2 ORF6 protein, providing a mechanistic link. SARS-CoV-2 ORF6 hampers type II interferon-mediated STAT1 signaling, resulting in diminished upregulation of NLRC5 and IRF1 gene expression. Moreover, SARS-CoV-2 ORF6 inhibits NLRC5 function via blocking karyopherin complex-dependent nuclear import of NLRC5. Collectively, our study uncovers an immune evasion mechanism of SARS-CoV-2 that targets the function of key MHC class I transcriptional regulators, STAT1-IRF1-NLRC5.
|
| 巻・号 |
12(1)
|
| ページ |
6602
|
| 公開日 |
2021-11-15
|
| DOI |
10.1038/s41467-021-26910-8
|
| PII |
10.1038/s41467-021-26910-8
|
| PMID |
34782627
|
| PMC |
PMC8594428
|
| MeSH |
COVID-19 / genetics
COVID-19 / immunology*
COVID-19 / pathology
COVID-19 / virology
Cell Line
Female
Gene Expression Regulation
Genes, MHC Class I / immunology*
Humans
Interferon Regulatory Factor-1 / antagonists & inhibitors*
Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
Male
Middle Aged
SARS-CoV-2 / genetics*
SARS-CoV-2 / isolation & purification
STAT1 Transcription Factor / antagonists & inhibitors*
Signal Transduction
Viral Proteins / immunology
Viral Proteins / metabolism*
|
| IF |
12.121
|
| リソース情報 |
| ヒト・動物細胞 |
A549(RCB0098)
CACO-2(RCB0988) |
