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

Pech, M; Weckmann, M; König, IR; Franke, A; Heinsen, FA; Oliver, B; Ricklefs, I; Fuchs, O; Rabe, K; Hansen, G; Mutius, EV; Kopp, MV

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

Pech, M Weckmann, M König, IR Franke, A Heinsen, FA Oliver, B

Ricklefs, I Fuchs, O Rabe, K Hansen, G Mutius, EV Kopp, MV

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Publication Type:: Journal Article
Citation:: PLoS ONE, 2018, 13 (11)
Issue Date:: 2018-11-01

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Field	Value	Language
dc.contributor.author	Pech, M	en_US
dc.contributor.author	Weckmann, M	en_US
dc.contributor.author	König, IR	en_US
dc.contributor.author	Franke, A	en_US
dc.contributor.author	Heinsen, FA	en_US
dc.contributor.author	Oliver, B https://orcid.org/0000-0002-7122-9262	en_US
dc.contributor.author	Ricklefs, I	en_US
dc.contributor.author	Fuchs, O	en_US
dc.contributor.author	Rabe, K	en_US
dc.contributor.author	Hansen, G	en_US
dc.contributor.author	Mutius, EV	en_US
dc.contributor.author	Kopp, MV	en_US
dc.date.available	2018-09-21	en_US
dc.date.issued	2018-11-01	en_US
dc.identifier.citation	PLoS ONE, 2018, 13 (11)	en_US
dc.identifier.uri	http://hdl.handle.net/10453/129249
dc.description.abstract	© 2018 Pech et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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 Human-Methylation450 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.	en_US
dc.relation	http://purl.org/au-research/grants/nhmrc/APP1026880
dc.relation	http://purl.org/au-research/grants/nhmrc/APP1110368
dc.relation.ispartof	PLoS ONE	en_US
dc.relation.isbasedon	10.1371/journal.pone.0205275	en_US
dc.subject.classification	General Science & Technology	en_US
dc.subject.mesh	Nasal Mucosa	en_US
dc.subject.mesh	Epithelial Cells	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Rhinovirus	en_US
dc.subject.mesh	Picornaviridae Infections	en_US
dc.subject.mesh	Asthma	en_US
dc.subject.mesh	RNA, Messenger	en_US
dc.subject.mesh	Case-Control Studies	en_US
dc.subject.mesh	Reproducibility of Results	en_US
dc.subject.mesh	DNA Methylation	en_US
dc.subject.mesh	Gene Expression Regulation	en_US
dc.subject.mesh	Down-Regulation	en_US
dc.subject.mesh	Up-Regulation	en_US
dc.subject.mesh	CpG Islands	en_US
dc.subject.mesh	Models, Biological	en_US
dc.subject.mesh	Adolescent	en_US
dc.subject.mesh	Child	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Chemokine CCL5	en_US
dc.subject.mesh	Biomarkers	en_US
dc.title	Rhinovirus infections change DNA methylation and mRNA expression in children with asthma	en_US
dc.type	Journal Article
utslib.citation.volume	11	en_US
utslib.citation.volume	13	en_US
utslib.for	1102 Cardiorespiratory Medicine and Haematology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access
pubs.issue	11	en_US
pubs.publication-status	Published	en_US
pubs.volume	13	en_US

Abstract:

© 2018 Pech et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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 Human-Methylation450 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.

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http://hdl.handle.net/10453/129249