The immune evasion mechanism of SARS-CoV-2 targeting the MHC class I pathway
| Project/Area Number |
21K15445
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49060:Virology-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
劉 知昇 北海道大学, 医学研究院, 助教 (30843437)
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| Project Period (FY) |
2021-04-01 – 2022-03-31
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| Project Status |
Discontinued (Fiscal Year 2021)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | SARS-COV-2 / ORF6 / MHC class I / NLRC5 / STAT1 / IRF1 / Karyopherin / COVID-19 / SARS-CoV-2 / Innate immunity |
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| Outline of Research at the Start |
Recent studies have been mainly focusing on type I or type III IFN responses triggered by SARS-CoV-2 infection. However, currently there is no study on the MHC class I pathway regulated by SARS-CoV-2. Our study is to investigate whether SARS-CoV-2 can suppress the host antigen-presenting pathways by scrutinizing the cellular signaling pathways that are essential for inducing MHC class I activation.
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| Outline of Annual Research Achievements |
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.
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