| Author | Francisco Junior, Ronaldo da Silva | |
| Author | Temerozo, Jairo R. | |
| Author | Ferreira, Cristina dos Santos | |
| Author | Martins, Yasmmin | |
| Author | Souza, Thiago Moreno L. | |
| Author | Medina-Acosta, Enrique | |
| Author | Vasconcelos, Ana Tereza Ribeiro de | |
| Access date | 2023-04-23T22:47:27Z | |
| Available date | 2023-04-23T22:47:27Z | |
| Document date | 2023 | |
| Citation | 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. | en_US |
| ISSN | 1664-3224 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/57916 | |
| Language | eng | en_US |
| Publisher | Frontiers Media | en_US |
| Rights | open access | |
| Subject in Portuguese | COVID-19 | en_US |
| Subject in Portuguese | Expressão do haplótipo | en_US |
| Subject in Portuguese | Troca de alelos | en_US |
| Subject in Portuguese | Alelos HLA | en_US |
| Subject in Portuguese | RNA-Seq, | en_US |
| Subject in Portuguese | SARS-CoV-2 | en_US |
| Subject in Portuguese | Expressão específica de alelo | en_US |
| Title | Differential haplotype expression in class I MHC genes during SARS-CoV-2 infection of human lung cell lines | en_US |
| Type | Article | |
| DOI | 10.3389/fimmu.2022.1101526 | |
| Abstract | 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. | en_US |
| Affilliation | Laboratório de Bioinformática (LABINFO), Laboratório Nacional de Computação Científica (LNCC/ MCTIC), Petrópolis, RJ, Brasil. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | Laboratório de Bioinformática (LABINFO), Laboratório Nacional de Computação Científica (LNCC/ MCTIC), Petrópolis, RJ, Brasil. | en_US |
| Affilliation | Instituto de Cálculo, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (FCEyN-UBA), Buenos Aires, Argentina. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | Laboratório de Bioinformática (LABINFO), Laboratório Nacional de Computação Científica (LNCC/ MCTIC), Petrópolis, RJ, Brasil. | en_US |
| Subject | Allele-specific expression | en_US |
| Subject | Allele swapping | en_US |
| Subject | COVID-19 | en_US |
| Subject | Haplotype expression | en_US |
| Subject | HLA alleles | en_US |
| Subject | RNA-Seq, | en_US |
| Subject | SARS-CoV-2 | en_US |
