Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants
Moriyama, M; Lucas, C; Monteiro, VS; , Proceedings of the National Academy of Sciences of the United States of America
Published
April 2023
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) possess mutations that confer resistance to neutralizing antibodies within the Spike protein and are associated with breakthrough infection and reinfection. By contrast, less is known about the escape from CD8+ T cell-mediated immunity by VOC. Here, we demonstrated that all SARS-CoV-2 VOCs possess the ability to suppress major histocompatibility complex class I (MHC-I) expression. We identified several viral genes that contribute to the suppression of MHC I expression. Notably, MHC-I upregulation was strongly inhibited after SARS-CoV-2 but not influenza virus infection in vivo. While earlier VOCs possess similar capacity as the ancestral strain to suppress MHC-I, the Omicron subvariants exhibited a greater ability to suppress surface MHC-I expression. We identified a common mutation in the E protein of Omicron that further suppressed MHC-I expression. Collectively, our data suggest that in addition to escaping from neutralizing antibodies, the success of Omicron subvariants to cause breakthrough infection and reinfection may in part be due to its optimized evasion from T cell recognition.
Authors
Miyu Moriyama, Carolina Lucas, Valter Silva Monteiro; Yale SARS-CoV-2 Genomic Surveillance Initiative; Akiko Iwasaki
Keywords
CD8 T cell; COVID-19; MHC; cytotoxic T lymphocytes; viral evasion