Journal Article

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

Yan, Shumei, Li, Rong, Zhang, Hui, Chen, Jingliang, Luo, Baohong, Ma, Xiancai, Yang, Tao, Zhang, Yiwen, Liu, Bingfeng, Xia, Baijin, Zhang, Xu, Zhang, Junsong, Chen, Yingshi, Huang, Feng, Huang, Wenjing, Xiao, Fei, Song, Zheng, Yu, Fei, Wu, Liyang, Li, Yuzhuang, Yuan, Yaochang, He, Xin, Liu, Jun, Pan, Ting

2021

Overview

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.

• Publisher: National Academy of Sciences
• Subject: Animals / Antigen Presentation / Antigens / Autophagy / Autophagy - genetics / Autophagy - immunology / Biological Sciences / Chlorocebus aethiops / Coronaviruses / COVID-19 / COVID-19 - genetics / COVID-19 - immunology / Cytotoxicity / Down-Regulation - immunology / Gene sequencing / HEK293 Cells / Histocompatibility Antigens Class I - genetics / Histocompatibility Antigens Class I - immunology / Homology / Humans / Immune Evasion / Immunosurveillance / Lymphocytes / Lymphocytes T / Lysis / Lysosomes / Lysosomes - genetics / Lysosomes - immunology / Lysosomes - virology / Major histocompatibility complex / Mice / Mice, Transgenic / Microbiology / Pandemics / Phagocytosis / Proteins / SARS-CoV-2 - genetics / SARS-CoV-2 - immunology / Severe acute respiratory syndrome coronavirus 2 / Vero Cells / Viral diseases / Viral Proteins - genetics / Viral Proteins - immunology