Allelic imbalance of HLA-B expression in human lung cells infected with coronavirus and other respiratory viruses

Autor: Yuanxu Zhang, Yisheng Sun, Hanping Zhu, Hai Hong, Jianmin Jiang, Pingping Yao, Huaxin Liao, Yanfeng Zhang
Rok vydání: 2022
Předmět:
Zdroj: European Journal of Human Genetics. 30:922-929
ISSN: 1476-5438
1018-4813
DOI: 10.1038/s41431-022-01070-5
Popis: The human leucocyte antigen (HLA) loci have been widely characterized to be associated with viral infectious diseases using either HLA allele frequency-based association or in silico predicted studies. However, there is less experimental evidence to link the HLA alleles with COVID-19 and other respiratory infectious diseases, particularly in the lung cells. To examine the role of HLA alleles in response to coronavirus and other respiratory viral infections in disease-relevant cells, we designed a two-stage study by integrating publicly accessible RNA-seq data sets, and performed allelic expression (AE) analysis on heterozygous HLA genotypes. We discovered an increased AE pattern accompanied with overexpression of HLA-B gene in SARS-CoV-2-infected human lung epithelial cells. Analysis of independent data sets verified the respiratory virus-induced AE of HLA-B gene in lung cells and tissues. The results were further experimentally validated in cultured lung cells infected with SARS-CoV-2. We further uncovered that the antiviral cytokine IFNβ contribute to AE of the HLA-B gene in lung cells. Our analyses provide a new insight into allelic influence on the HLA expression in association with SARS-CoV-2 and other common viral infectious diseases.
Databáze: OpenAIRE
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