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

Pech, Martin; Weckmann, Markus; König, Inke R; Franke, Andre; Heinsen, Femke-Anouska; Oliver, Brian; Ricklefs, Isabell; Fuchs, Oliver; Rabe, Klaus; Hansen, Gesine; V Mutius, Erika; Kopp, Matthias V (2018). Rhinovirus infections change DNA methylation and mRNA expression in children with asthma. PLoS ONE, 13(11), e0205275. Public Library of Science 10.1371/journal.pone.0205275

[img]
Preview
Text
journal.pone.0205275.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (1MB) | Preview

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine

UniBE Contributor:

Fuchs, Oliver

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Karen Lidzba

Date Deposited:

20 Aug 2019 15:56

Last Modified:

06 Jan 2020 11:01

Publisher DOI:

10.1371/journal.pone.0205275

PubMed ID:

30485264

BORIS DOI:

10.7892/boris.131507

URI:

https://boris.unibe.ch/id/eprint/131507

Actions (login required)

Edit item Edit item
Provide Feedback