LAUSR

Significance As part of the adaptive immune response, virus-infected cells present virus-derived peptides to cytotoxic T cells on the surface of infected cells, using a protein complex termed major histocompatibility complex class-I. Some viruses counteract antigen presentation by depleting major histocompatibility complex class-I from the cell surface. We show that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) uses an accessory protein ORF7a to interfere with the formation of peptide-major histocompatibility complex class-I complexes, prevent their movement to the cell surface, and thus inhibit antigen presentation to cytotoxic T cells. ORF7a proteins from SARS-CoV-2-related viruses vary in their ability to interfere with antigen presentation, which might affect the ability of vaccine- or infection-elicited immune responses to protect against this family of pandemic threat viruses.