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HLA-C dysregulation as a possible mechanism of immune evasion in SARS-CoV-2 and other RNA-virus infections

One of the mechanisms by which viruses can evade the host’s immune system is to modify the host’s DNA methylation pattern. This work aims to investigate the DNA methylation and gene expression profile of COVID-19 patients, divided into symptomatic and asymptomatic, and healthy controls, focusing on...

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Autores principales: Loi, Eleonora, Moi, Loredana, Cabras, Paola, Arduino, Giulia, Costanzo, Giulia, Del Giacco, Stefano, Erlich, Henry A., Firinu, Davide, Caddori, Aldo, Zavattari, Patrizia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9618630/
https://www.ncbi.nlm.nih.gov/pubmed/36325330
http://dx.doi.org/10.3389/fimmu.2022.1011829
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author Loi, Eleonora
Moi, Loredana
Cabras, Paola
Arduino, Giulia
Costanzo, Giulia
Del Giacco, Stefano
Erlich, Henry A.
Firinu, Davide
Caddori, Aldo
Zavattari, Patrizia
author_facet Loi, Eleonora
Moi, Loredana
Cabras, Paola
Arduino, Giulia
Costanzo, Giulia
Del Giacco, Stefano
Erlich, Henry A.
Firinu, Davide
Caddori, Aldo
Zavattari, Patrizia
author_sort Loi, Eleonora
collection PubMed
description One of the mechanisms by which viruses can evade the host’s immune system is to modify the host’s DNA methylation pattern. This work aims to investigate the DNA methylation and gene expression profile of COVID-19 patients, divided into symptomatic and asymptomatic, and healthy controls, focusing on genes involved in the immune response. In this study, changes in the methylome of COVID-19 patients’ upper airways cells, the first barrier against respiratory infections and the first cells presenting viral antigens, are shown for the first time. Our results showed alterations in the methylation pattern of genes encoding proteins implicated in the response against pathogens, in particular the HLA-C gene, also important for the T-cell mediated memory response. HLA-C expression significantly decreases in COVID-19 patients, especially in those with a more severe prognosis and without other possibly confounding co-morbidities. Moreover, our bionformatic analysis revealed that the identified methylation alteration overlaps with enhancers regulating HLA-C expression, suggesting an additional mechanism exploited by SARS-CoV-2 to inhibit this fundamental player in the host’s immune response. HLA-C could therefore represent both a prognostic marker and an excellent therapeutic target, also suggesting a preventive intervention that conjugate a virus-specific antigenic stimulation with an adjuvant increasing the T-cell mediated memory response.
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spelling pubmed-96186302022-11-01 HLA-C dysregulation as a possible mechanism of immune evasion in SARS-CoV-2 and other RNA-virus infections Loi, Eleonora Moi, Loredana Cabras, Paola Arduino, Giulia Costanzo, Giulia Del Giacco, Stefano Erlich, Henry A. Firinu, Davide Caddori, Aldo Zavattari, Patrizia Front Immunol Immunology One of the mechanisms by which viruses can evade the host’s immune system is to modify the host’s DNA methylation pattern. This work aims to investigate the DNA methylation and gene expression profile of COVID-19 patients, divided into symptomatic and asymptomatic, and healthy controls, focusing on genes involved in the immune response. In this study, changes in the methylome of COVID-19 patients’ upper airways cells, the first barrier against respiratory infections and the first cells presenting viral antigens, are shown for the first time. Our results showed alterations in the methylation pattern of genes encoding proteins implicated in the response against pathogens, in particular the HLA-C gene, also important for the T-cell mediated memory response. HLA-C expression significantly decreases in COVID-19 patients, especially in those with a more severe prognosis and without other possibly confounding co-morbidities. Moreover, our bionformatic analysis revealed that the identified methylation alteration overlaps with enhancers regulating HLA-C expression, suggesting an additional mechanism exploited by SARS-CoV-2 to inhibit this fundamental player in the host’s immune response. HLA-C could therefore represent both a prognostic marker and an excellent therapeutic target, also suggesting a preventive intervention that conjugate a virus-specific antigenic stimulation with an adjuvant increasing the T-cell mediated memory response. Frontiers Media S.A. 2022-10-17 /pmc/articles/PMC9618630/ /pubmed/36325330 http://dx.doi.org/10.3389/fimmu.2022.1011829 Text en Copyright © 2022 Loi, Moi, Cabras, Arduino, Costanzo, Del Giacco, Erlich, Firinu, Caddori and Zavattari https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Loi, Eleonora
Moi, Loredana
Cabras, Paola
Arduino, Giulia
Costanzo, Giulia
Del Giacco, Stefano
Erlich, Henry A.
Firinu, Davide
Caddori, Aldo
Zavattari, Patrizia
HLA-C dysregulation as a possible mechanism of immune evasion in SARS-CoV-2 and other RNA-virus infections
title HLA-C dysregulation as a possible mechanism of immune evasion in SARS-CoV-2 and other RNA-virus infections
title_full HLA-C dysregulation as a possible mechanism of immune evasion in SARS-CoV-2 and other RNA-virus infections
title_fullStr HLA-C dysregulation as a possible mechanism of immune evasion in SARS-CoV-2 and other RNA-virus infections
title_full_unstemmed HLA-C dysregulation as a possible mechanism of immune evasion in SARS-CoV-2 and other RNA-virus infections
title_short HLA-C dysregulation as a possible mechanism of immune evasion in SARS-CoV-2 and other RNA-virus infections
title_sort hla-c dysregulation as a possible mechanism of immune evasion in sars-cov-2 and other rna-virus infections
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9618630/
https://www.ncbi.nlm.nih.gov/pubmed/36325330
http://dx.doi.org/10.3389/fimmu.2022.1011829
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