The immune evasion mechanism of SARS-CoV-2 targeting the MHC class I pathway

SARS-CoV-2针对MHC I类通路的免疫逃避机制

• 批准号: 21K15445
• 负责人: 劉 知昇
• 金额: $ 3万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K15445/
• 关键词: SARS-COV-2; ORF6; MHC class I; NLRC5; STAT1; IRF1; Karyopherin; COVID-19; SARS-CoV-2; Innate immunity

My research goal for year 2021-2022 was to identify the SARS-CoV-2 viral factor(s) that inhibit a host immune program, especially the MHC class I pathway. During this period, I have successfully identified that SARS-CoV-2 viral factor, ORF6, can efficiently suppress the MHC class I pathway. Moreover, I elucidated the molecular mechanism for this inhibition. SARS-CoV-2 ORF6 can block Type II interferon signaling pathway, which is critical for the MHC class I activation, through inhibiting STAT1-IRF1 signaling axis. Furthermore, I found that SARS-CoV-2 ORF6 inhibits the function of NLRC5, a master transactivator of the MHC class I pathway, by hampering the nuclear translocation of NLRC5. With these findings, I published my research to the Nature Communications journal in November, 2021.

我在2021 - 2022年的研究目标是确定抑制宿主免疫程序的SARS-COV-2病毒因子，尤其是MHC I类途径。在此期间，我成功地确定SARS-COV-2病毒因子ORF6可以有效抑制MHC I类途径。此外，我阐明了这种抑制的分子机制。 SARS-COV-2 ORF6可以通过抑制STAT1-IRF1信号轴来阻止II型干扰素信号通路，这对于MHC I类激活至关重要。此外，我发现SARS-COV-2 ORF6通过阻碍NLRC5的核转运来抑制MHC I类途径的主要反式激活剂NLRC5的功能。有了这些发现，我于2021年11月向《自然通信杂志》发表了研究。