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The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-Ι.
- Source :
- Proceedings of the National Academy of Sciences of the United States of America; 6/8/2021, Vol. 118 Issue 23, p1-12, 12p
- Publication Year :
- 2021
-
Abstract
- COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic and has claimed over 2 million lives worldwide. Although the genetic sequences of SARS-CoV and SARS-CoV-2 have high homology, the clinical and pathological characteristics of COVID-19 differ significantly from those of SARS. How and whether SARS-CoV-2 evades (cellular) immune surveillance requires further elucidation. In this study, we show that SARS-CoV-2 infection leads to major histocompability complex class Ι (MHC-Ι) down-regulation both in vitro and in vivo. The viral protein encoded by open reading frame 8 (ORF8) of SARS-CoV-2, which shares the least homology with SARS-CoV among all viral proteins, directly interacts with MHC-Ι molecules and mediates their down-regulation. In ORF8-expressing cells, MHC-Ι molecules are selectively targeted for lysosomal degradation via autophagy. Thus, SARS-CoV-2–infected cells are much less sensitive to lysis by cytotoxic T lymphocytes. Because ORF8 protein impairs the antigen presentation system, inhibition of ORF8 could be a strategy to improve immune surveillance. [ABSTRACT FROM AUTHOR]
- Subjects :
- SARS-CoV-2
CYTOTOXIC T cells
COVID-19
COMMERCIAL products
VIRAL proteins
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 118
- Issue :
- 23
- Database :
- Complementary Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 151031247
- Full Text :
- https://doi.org/10.1073/pnas.2024202118