In this preprint, Zhang et al. elucidate a potential immune evasion strategy involving the SARS-CoV-2 ORF8 protein. They show that expression of ORF8, which directly binds to MHC class I molecules, downregulates their surface expression on HEK293T cells. ORF8 co-localizes with MHC class I molecules in lysosomes, thereby disrupting antigen presentation. When healthy human donor-derived cytotoxic T lymphocytes (CTLs) sensitized to the SARS-CoV-2 epitope SSp-1 were exposed to autologous dendritic cells pre-pulsed with SSp-1, there was reduced killing of ORF8-expressing HEK293T cells compared with ORF8 non-expressing cells. These results were replicated using CTLs isolated from a patient recovering from COVID-19 that responded to a mixture of SARS-CoV-2 N and S proteins. This potential mechanism for SARS-CoV-2 evasion of host immune surveillance warrants further investigation.
Competing interests
The author declares no competing interests.
References
Original article
- Zhang Y, et al. The ORF8 protein of SARS-CoV-2 mediates immune evasion through potently downregulating MHC-I. bioRxiv. 2020 doi: 10.1101/2020.05.24.111823. [DOI] [Google Scholar]