論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1119 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 6.2 |
| リソース情報 | |
| ヒト・動物細胞 | A549(RCB0098) CACO-2(RCB0988) HuH-7 |