%0 Journal Article %A Zhang, Yiwen %A Zhang, Junsong %A Chen, Yingshi %A Luo, Baohong %A Yuan, Yaochang %A Huang, Feng %A Yang, Tao %A Yu, Fei %A Liu, Jun %A Liu, Bingfen %A Song, Zheng %A Chen, Jingliang %A Pan, Ting %A Zhang, Xu %A Li, Yuzhuang %A Li, Rong %A Huang, Wenjing %A Xiao, Fei %A Zhang, Hui %T The ORF8 Protein of SARS-CoV-2 Mediates Immune Evasion through Potently Downregulating MHC-I %D 2020 %R 10.1101/2020.05.24.111823 %J bioRxiv %P 2020.05.24.111823 %X SARS-CoV-2 infection have caused global pandemic and claimed over 5,000,000 tolls1–4. Although the genetic sequences of their etiologic viruses are of high homology, the clinical and pathological characteristics of COVID-19 significantly differ from SARS5,6. Especially, it seems that SARS-CoV-2 undergoes vast replication in vivo without being effectively monitored by anti-viral immunity7. 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 CTLs8. 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.Competing Interest StatementThe authors have declared no competing interest. %U https://www.biorxiv.org/content/biorxiv/early/2020/05/24/2020.05.24.111823.full.pdf