tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2021 Jun 8;118(23):e2024202118.
doi: 10.1073/pnas.2024202118.
The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-?
Yiwen Zhang[SUP] 1 [/SUP], Yingshi Chen[SUP] 1 [/SUP], Yuzhuang Li[SUP] 1 [/SUP], Feng Huang[SUP] 2 [/SUP], Baohong Luo[SUP] 1 [/SUP], Yaochang Yuan[SUP] 1 [/SUP], Baijin Xia[SUP] 1 [/SUP], Xiancai Ma[SUP] 1 [/SUP], Tao Yang[SUP] 1 [/SUP], Fei Yu[SUP] 1 [/SUP], Jun Liu[SUP] 1 [/SUP], Bingfeng Liu[SUP] 1 [/SUP], Zheng Song[SUP] 1 [/SUP], Jingliang Chen[SUP] 1 [/SUP], Shumei Yan[SUP] 1 [/SUP], Liyang Wu[SUP] 1 [/SUP], Ting Pan[SUP] 1 [/SUP], Xu Zhang[SUP] 1 [/SUP], Rong Li[SUP] 1 [/SUP], Wenjing Huang[SUP] 3 [/SUP], Xin He[SUP] 1 [/SUP], Fei Xiao[SUP] 4 [/SUP], Junsong Zhang[SUP] 5 [/SUP], Hui Zhang[SUP] 6 [/SUP]
Affiliations
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 ? (MHC-?) 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-? molecules and mediates their down-regulation. In ORF8-expressing cells, MHC-? 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: MHC-?; ORF8; SARS-CoV-2; immune evasion.
. 2021 Jun 8;118(23):e2024202118.
doi: 10.1073/pnas.2024202118.
The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-?
Yiwen Zhang[SUP] 1 [/SUP], Yingshi Chen[SUP] 1 [/SUP], Yuzhuang Li[SUP] 1 [/SUP], Feng Huang[SUP] 2 [/SUP], Baohong Luo[SUP] 1 [/SUP], Yaochang Yuan[SUP] 1 [/SUP], Baijin Xia[SUP] 1 [/SUP], Xiancai Ma[SUP] 1 [/SUP], Tao Yang[SUP] 1 [/SUP], Fei Yu[SUP] 1 [/SUP], Jun Liu[SUP] 1 [/SUP], Bingfeng Liu[SUP] 1 [/SUP], Zheng Song[SUP] 1 [/SUP], Jingliang Chen[SUP] 1 [/SUP], Shumei Yan[SUP] 1 [/SUP], Liyang Wu[SUP] 1 [/SUP], Ting Pan[SUP] 1 [/SUP], Xu Zhang[SUP] 1 [/SUP], Rong Li[SUP] 1 [/SUP], Wenjing Huang[SUP] 3 [/SUP], Xin He[SUP] 1 [/SUP], Fei Xiao[SUP] 4 [/SUP], Junsong Zhang[SUP] 5 [/SUP], Hui Zhang[SUP] 6 [/SUP]
Affiliations
- PMID: 34021074
- DOI: 10.1073/pnas.2024202118
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 ? (MHC-?) 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-? molecules and mediates their down-regulation. In ORF8-expressing cells, MHC-? 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: MHC-?; ORF8; SARS-CoV-2; immune evasion.