Differential haplotype expression in class I MHC genes during SARS-CoV-2 infection of human lung cell lines

Detalhes bibliográficos
Autor(a) principal: Francisco Junior, Ronaldo da Silva
Data de Publicação: 2023
Outros Autores: Temerozo, Jairo R., Ferreira, Cristina dos Santos, Martins, Yasmmin, Souza, Thiago Moreno L., Medina-Acosta, Enrique, Vasconcelos, Ana Tereza Ribeiro de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/57916
Resumo: Laboratório de Bioinformática (LABINFO), Laboratório Nacional de Computação Científica (LNCC/ MCTIC), Petrópolis, RJ, Brasil.
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spelling Francisco Junior, Ronaldo da SilvaTemerozo, Jairo R.Ferreira, Cristina dos SantosMartins, YasmminSouza, Thiago Moreno L.Medina-Acosta, EnriqueVasconcelos, Ana Tereza Ribeiro de2023-04-23T22:47:27Z2023-04-23T22:47:27Z2023FRANCISCO JUNIOR, Ronaldo da Silva et al. Differential haplotype expression in class I MHC genes during SARS-CoV-2 infection of human lung cell lines. Frontiers in Immunology, n.13:1101526, p. 1 - 16, Feb. 2023.1664-3224https://www.arca.fiocruz.br/handle/icict/5791610.3389/fimmu.2022.1101526engFrontiers MediaCOVID-19Expressão do haplótipoTroca de alelosAlelos HLARNA-Seq,SARS-CoV-2Expressão específica de aleloAllele-specific expressionAllele swappingCOVID-19Haplotype expressionHLA allelesRNA-Seq,SARS-CoV-2Differential haplotype expression in class I MHC genes during SARS-CoV-2 infection of human lung cell linesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleLaboratório de Bioinformática (LABINFO), Laboratório Nacional de Computação Científica (LNCC/ MCTIC), Petrópolis, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Laboratório de Bioinformática (LABINFO), Laboratório Nacional de Computação Científica (LNCC/ MCTIC), Petrópolis, RJ, Brasil.Instituto de Cálculo, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (FCEyN-UBA), Buenos Aires, Argentina.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia de Inovação em Doenças Negligenciadas Populações Negligenciadas. Centro de Desenvolvimento Tecnológico em Saúde (CDTS). Rio de Janeiro, RJ, Brasil.Universidade Estadual do Norte Fluminense Darcy Ribeiro (UENF). Centro de Biociências e Biotecnologia. Unidade de Identificação e Diagnóstico Molecular (NUDIM), Laboratório de Biotecnologia. Campos dos Goytacazes, RJ, Brasil.Laboratório de Bioinformática (LABINFO), Laboratório Nacional de Computação Científica (LNCC/ MCTIC), Petrópolis, RJ, Brasil.Introduction: Cell entry of SARS-CoV-2 causes genome-wide disruption of the transcriptional profiles of genes and biological pathways involved in the pathogenesis of COVID-19. Expression allelic imbalance is characterized by a deviation from the Mendelian expected 1:1 expression ratio and is an important source of allele-specific heterogeneity. Expression allelic imbalance can be measured by allele-specific expression analysis (ASE) across heterozygous informative expressed single nucleotide variants (eSNVs). ASE reflects many regulatory biological phenomena that can be assessed by combining genome and transcriptome information. ASE contributes to the interindividual variability associated with the disease. We aim to estimate the transcriptome-wide impact of SARS-CoV-2 infection by analyzing eSNVs. Methods: We compared ASE profiles in the human lung cell lines Calu-3, A459, and H522 before and after infection with SARS-CoV-2 using RNA-Seq experiments. Results: We identified 34 differential ASE (DASE) sites in 13 genes (HLA-A, HLAB, HLA-C, BRD2, EHD2, GFM2, GSPT1, HAVCR1, MAT2A, NQO2, SUPT6H, TNFRSF11A, UMPS), all of which are enriched in protein binding functions and play a role in COVID-19. Most DASE sites were assigned to the MHC class I locus and were predominantly upregulated upon infection. DASE sites in the MHC class I locus also occur in iPSC-derived airway epithelium basal cells infected with SARS-CoV-2. Using an RNA-Seq haplotype reconstruction approach, we found DASE sites and adjacent eSNVs in phase (i.e., predicted on the same DNA strand), demonstrating differential haplotype expression upon infection. We found a bias towards the expression of the HLA alleles with a higher binding affinity to SARS-CoV-2 epitopes. Discussion: Independent of gene expression compensation, SARS-CoV-2 infection of human lung cell lines induces transcriptional allelic switching at the MHC loci. This suggests a response mechanism to SARS-CoV-2 infection that swaps HLA alleles with poor epitope binding affinity, an expectation supported by publicly available proteome data.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/57916/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALThiagoSouza_JairoTemeroso_etal_IOC_2023.pdfThiagoSouza_JairoTemeroso_etal_IOC_2023.pdfapplication/pdf3872174https://www.arca.fiocruz.br/bitstream/icict/57916/2/ThiagoSouza_JairoTemeroso_etal_IOC_2023.pdf5e4c61becf97f59b84424e56a85d4ce7MD52icict/579162023-09-04 11:30:01.057oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-09-04T14:30:01Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.en_US.fl_str_mv Differential haplotype expression in class I MHC genes during SARS-CoV-2 infection of human lung cell lines
title Differential haplotype expression in class I MHC genes during SARS-CoV-2 infection of human lung cell lines
spellingShingle Differential haplotype expression in class I MHC genes during SARS-CoV-2 infection of human lung cell lines
Francisco Junior, Ronaldo da Silva
COVID-19
Expressão do haplótipo
Troca de alelos
Alelos HLA
RNA-Seq,
SARS-CoV-2
Expressão específica de alelo
Allele-specific expression
Allele swapping
COVID-19
Haplotype expression
HLA alleles
RNA-Seq,
SARS-CoV-2
title_short Differential haplotype expression in class I MHC genes during SARS-CoV-2 infection of human lung cell lines
title_full Differential haplotype expression in class I MHC genes during SARS-CoV-2 infection of human lung cell lines
title_fullStr Differential haplotype expression in class I MHC genes during SARS-CoV-2 infection of human lung cell lines
title_full_unstemmed Differential haplotype expression in class I MHC genes during SARS-CoV-2 infection of human lung cell lines
title_sort Differential haplotype expression in class I MHC genes during SARS-CoV-2 infection of human lung cell lines
author Francisco Junior, Ronaldo da Silva
author_facet Francisco Junior, Ronaldo da Silva
Temerozo, Jairo R.
Ferreira, Cristina dos Santos
Martins, Yasmmin
Souza, Thiago Moreno L.
Medina-Acosta, Enrique
Vasconcelos, Ana Tereza Ribeiro de
author_role author
author2 Temerozo, Jairo R.
Ferreira, Cristina dos Santos
Martins, Yasmmin
Souza, Thiago Moreno L.
Medina-Acosta, Enrique
Vasconcelos, Ana Tereza Ribeiro de
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Francisco Junior, Ronaldo da Silva
Temerozo, Jairo R.
Ferreira, Cristina dos Santos
Martins, Yasmmin
Souza, Thiago Moreno L.
Medina-Acosta, Enrique
Vasconcelos, Ana Tereza Ribeiro de
dc.subject.other.en_US.fl_str_mv COVID-19
Expressão do haplótipo
Troca de alelos
Alelos HLA
RNA-Seq,
SARS-CoV-2
Expressão específica de alelo
topic COVID-19
Expressão do haplótipo
Troca de alelos
Alelos HLA
RNA-Seq,
SARS-CoV-2
Expressão específica de alelo
Allele-specific expression
Allele swapping
COVID-19
Haplotype expression
HLA alleles
RNA-Seq,
SARS-CoV-2
dc.subject.en.en_US.fl_str_mv Allele-specific expression
Allele swapping
COVID-19
Haplotype expression
HLA alleles
RNA-Seq,
SARS-CoV-2
description Laboratório de Bioinformática (LABINFO), Laboratório Nacional de Computação Científica (LNCC/ MCTIC), Petrópolis, RJ, Brasil.
publishDate 2023
dc.date.accessioned.fl_str_mv 2023-04-23T22:47:27Z
dc.date.available.fl_str_mv 2023-04-23T22:47:27Z
dc.date.issued.fl_str_mv 2023
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv FRANCISCO JUNIOR, Ronaldo da Silva et al. Differential haplotype expression in class I MHC genes during SARS-CoV-2 infection of human lung cell lines. Frontiers in Immunology, n.13:1101526, p. 1 - 16, Feb. 2023.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/57916
dc.identifier.issn.en_US.fl_str_mv 1664-3224
dc.identifier.doi.none.fl_str_mv 10.3389/fimmu.2022.1101526
identifier_str_mv FRANCISCO JUNIOR, Ronaldo da Silva et al. Differential haplotype expression in class I MHC genes during SARS-CoV-2 infection of human lung cell lines. Frontiers in Immunology, n.13:1101526, p. 1 - 16, Feb. 2023.
1664-3224
10.3389/fimmu.2022.1101526
url https://www.arca.fiocruz.br/handle/icict/57916
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/57916/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/57916/2/ThiagoSouza_JairoTemeroso_etal_IOC_2023.pdf
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repository.mail.fl_str_mv repositorio.arca@fiocruz.br
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