The ORF8 Protein of SARS-CoV-2 Mediates Immune Evasion through Potently Downregulating MHC-I
View ORCID ProfileYiwen Zhang, Junsong Zhang, Yingshi Chen, Baohong Luo, Yaochang Yuan, Feng Huang, Tao Yang, Fei Yu, Jun Liu, Bingfeng Liu, Zheng Song, Jingliang Chen, Ting Pan, Xu Zhang, Yuzhuang Li, Rong Li, Wenjing Huang, Fei Xiao, Hui Zhang
doi: https://doi.org/10.1101/2020.05.24.111823
Abstract
SARS-CoV-2 infection have caused global pandemic and claimed over 5,000,000 tolls. Although the genetic sequences of their etiologic viruses are of high homology, the clinical and pathological characteristics of COVID-19 significantly differ from SARS. Especially, it seems that SARS-CoV-2 undergoes vast replication in vivo without being effectively monitored by anti-viral immunity. Here, we show that the viral protein encoded from open reading frame 8 (ORF8) of SARS-CoV-2, which shares the least homology with SARS-CoV among all the viral proteins, can directly interact with MHC-I molecules and significantly down-regulates their surface expression on various cell types. In contrast, ORF8a and ORF8b of SARS-CoV do not exert this function. In the ORF8-expressing cells, MHC-I molecules are selectively target for lysosomal degradation by an autophagy-dependent mechanism. As a result, CTLs inefficiently eliminate the ORF8-expressing cells. Our results demonstrate that ORF8 protein disrupts antigen presentation and reduces the recognition and the elimination of virus-infected cells by CTLs. Therefore, we suggest that the inhibition of ORF8 function could be a strategy to improve the special immune surveillance and accelerate the eradication of SARS-CoV-2 in vivo.
