The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-Ι

Yiwen Zhang, Yingshi Chen, Yuzhuang Li, Feng Huang, Baohong Luo, Yaochang Yuan, Baijin Xia, Xiancai Ma, Tao Yang, Fei Yu, Jun Liu, Bingfeng Liu (+12 others)
2021 Proceedings of the National Academy of Sciences of the United States of America  
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
more » ... 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.
doi:10.1073/pnas.2024202118 pmid:34021074 fatcat:kzrxfj4vsbh7lcmmvbi6lkg3n4