RT Journal Article
SR Electronic
T1 The ORF8 Protein of SARS-CoV-2 Mediates Immune Evasion through Potently Downregulating MHC-I
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.24.111823
DO 10.1101/2020.05.24.111823
A1 Yiwen Zhang
A1 Junsong Zhang
A1 Yingshi Chen
A1 Baohong Luo
A1 Yaochang Yuan
A1 Feng Huang
A1 Tao Yang
A1 Fei Yu
A1 Jun Liu
A1 Bingfen Liu
A1 Zheng Song
A1 Jingliang Chen
A1 Ting Pan
A1 Xu Zhang
A1 Yuzhuang Li
A1 Rong Li
A1 Wenjing Huang
A1 Fei Xiao
A1 Hui Zhang
YR 2020
UL http://biorxiv.org/content/early/2020/05/24/2020.05.24.111823.abstract
AB 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.