TY - JOUR T1 - The ORF8 Protein of SARS-CoV-2 Mediates Immune Evasion through Potently Downregulating MHC-I JF - bioRxiv DO - 10.1101/2020.05.24.111823 SP - 2020.05.24.111823 AU - Zhang, Yiwen AU - Zhang, Junsong AU - Chen, Yingshi AU - Luo, Baohong AU - Yuan, Yaochang AU - Huang, Feng AU - Yang, Tao AU - Yu, Fei AU - Liu, Jun AU - Liu, Bingfen AU - Song, Zheng AU - Chen, Jingliang AU - Pan, Ting AU - Zhang, Xu AU - Li, Yuzhuang AU - Li, Rong AU - Huang, Wenjing AU - Xiao, Fei AU - Zhang, Hui Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/05/24/2020.05.24.111823.abstract N2 - 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. ER -