Journal Article

Rhinovirus infections change DNA methylation and mRNA expression in children with asthma

König, Inke R., v. Mutius, Erika, Weckmann, Markus, Kopp, Matthias V., Pech, Martin, Heinsen, Femke-Anouska, Ricklefs, Isabell, Rabe, Klaus, Hansen, Gesine, Franke, Andre, Oliver, Brian, Fuchs, Oliver

2018

Overview

Human rhinovirus infection (HRVI) plays an important role in asthma exacerbations and is thought to be involved in asthma development during early childhood. We hypothesized that HRVI causes differential DNA methylation and subsequently differential mRNA expression in epithelial cells of children with asthma. Primary nasal epithelial cells from children with (n = 10) and without (n = 10) asthma were cultivated up to passage two and infected with Rhinovirus-16 (RV-16). HRVI-induced genome-wide differences of DNA methylation in asthmatics (vs. controls) and resulting mRNA expression were analyzed by the HumanMethylation450 BeadChip Kit (Illumina) and RNA sequencing. These results were further verified by pyrosequencing and quantitative PCR, respectively. 471 CpGs belonging to 268 genes were identified to have HRVI-induced asthma-specifically modified DNA methylation and mRNA expression. A minimum-change criteria was applied to restrict assessment of genes with changes in DNA methylation and mRNA expression of at least 3% and least 0.1 reads/kb per million mapped reads, respectively. Using this approach we identified 16 CpGs, including HLA-B-associated transcript 3 (BAT3) and Neuraminidase 1 (NEU1), involved in host immune response against HRVI. HRVI in nasal epithelial cells leads to specific modifications of DNA methylation with altered mRNA expression in children with asthma. The HRVI-induced alterations in DNA methylation occurred in genes involved in the host immune response against viral infections and asthma pathogenesis. The findings of our pilot study may partially explain how HRVI contribute to the persistence and progression of asthma, and aid to identify possible new therapeutic targets. The promising findings of this pilot study would benefit from replication in a larger cohort.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adolescent / Asthma / Asthma - genetics / Asthma - virology / Asthmatic persons / Biology and life sciences / Biomarkers - metabolism / Case-Control Studies / Chemokine CCL5 - genetics / Chemokine CCL5 - metabolism / Child / Child development / Childhood asthma / Children / Children & youth / CpG Islands - genetics / Deoxyribonucleic acid / Development and progression / DNA / DNA methylation / DNA Methylation - genetics / Down-Regulation - genetics / Epigenetics / Epithelial cells / Epithelial Cells - pathology / Epithelial Cells - virology / Exo-a-sialidase / Family medical history / Female / Fibroblasts / Gene expression / Gene Expression Regulation / Gene sequencing / Genes / Genomes / Genomics / Histocompatibility antigen HLA / HLA antigens / Humans / Immune response / Immune system / Infection / Infections / Inflammation / Male / Medical research / Medicine and Health Sciences / Messenger RNA / Methylation / Models, Biological / Molecular biology / Nasal Mucosa - pathology / Pathogenesis / Pediatrics / People and Places / Picornaviridae Infections - genetics / Picornaviridae Infections - virology / Polymerase chain reaction / Reproducibility of Results / Research and analysis methods / Rhinovirus / Rhinovirus - physiology / Ribonucleic acid / Risk factors / RNA / RNA sequencing / RNA, Messenger - genetics / RNA, Messenger - metabolism / Social Sciences / Target recognition / Therapeutic applications / Transcription / Up-Regulation - genetics / Viral infections