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Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants

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...

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Autores principales: Moriyama, Miyu, Lucas, Carolina, Monteiro, Valter Silva, Iwasaki, Akiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10120007/
https://www.ncbi.nlm.nih.gov/pubmed/37036977
http://dx.doi.org/10.1073/pnas.2221652120
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author Moriyama, Miyu
Lucas, Carolina
Monteiro, Valter Silva
Iwasaki, Akiko
author_facet Moriyama, Miyu
Lucas, Carolina
Monteiro, Valter Silva
Iwasaki, Akiko
author_sort Moriyama, Miyu
collection PubMed
description 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.
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spelling pubmed-101200072023-04-22 Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants Moriyama, Miyu Lucas, Carolina Monteiro, Valter Silva Iwasaki, Akiko Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2023-04-10 2023-04-18 /pmc/articles/PMC10120007/ /pubmed/37036977 http://dx.doi.org/10.1073/pnas.2221652120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Biological Sciences
Moriyama, Miyu
Lucas, Carolina
Monteiro, Valter Silva
Iwasaki, Akiko
Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants
title Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants
title_full Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants
title_fullStr Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants
title_full_unstemmed Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants
title_short Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants
title_sort enhanced inhibition of mhc-i expression by sars-cov-2 omicron subvariants
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10120007/
https://www.ncbi.nlm.nih.gov/pubmed/37036977
http://dx.doi.org/10.1073/pnas.2221652120
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