Abstract
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.
【초록키워드】 SARS-CoV-2, coronavirus, Diseases, Antiviral, cytokine, in silico, Antigen, cells, respiratory virus, human lung, epithelial cells, HLA, genotypes, expression, respiratory viral infection, respiratory viral infections, association, HLA-B, Analysis, leucocyte, tissues, HLA alleles, IFNβ, HLA allele, loci, RNA-seq data, viral infectious diseases, overexpression, lung cells, human lung epithelial cells, viral infectious disease, independent data set, heterozygous, experimental evidence, lung cell, predicted, performed, characterized, less, contribute, analysis, allelic, accompanied, infected with SARS-CoV-2, with COVID-19, 【제목키워드】 coronavirus, expression, other respiratory virus, human lung cell,