The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-Ι.
Proc Natl Acad Sci U S A
; 118(23)2021 06 08.
Article
in English
| MEDLINE | ID: covidwho-1238060
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Viral Proteins
/
Histocompatibility Antigens Class I
/
Down-Regulation
/
Antigen Presentation
/
Immune Evasion
/
SARS-CoV-2
/
COVID-19
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
Pnas.2024202118
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