title: Human rhinovirus infection causes different DNA methylation changes in nasal epithelial cells from healthy and asthmatic subjects.
abstract: BACKGROUND
  Mechanisms underlying the development of virus-induced asthma exacerbations remain unclear. To investigate if epigenetic mechanisms could be involved in virus-induced asthma exacerbations, we undertook DNA methylation profiling in asthmatic and healthy nasal epithelial cells (NECs) during Human Rhinovirus (HRV) infection in vitro.
  
  
  METHODS
  Global and loci-specific methylation profiles were determined via Alu element and Infinium Human Methylation 450 K microarray, respectively. Principal components analysis identified the genomic loci influenced the most by disease-status and infection. Real-time PCR and pyrosequencing were used to confirm gene expression and DNA methylation, respectively.
  
  
  RESULTS
  HRV infection significantly increased global DNA methylation in cells from asthmatic subjects only (43.6% to 44.1%, p = 0.04). Microarray analysis revealed 389 differentially methylated loci either based on disease status, or caused by virus infection. There were disease-associated DNA methylation patterns that were not affected by HRV infection as well as HRV-induced DNA methylation changes that were unique to each group. A common methylation locus stood out in response to HRV infection in both groups, where the small nucleolar RNA, H/ACA box 12 (SNORA12) is located. Further analysis indicated that a relationship existed between SNORA12 DNA methylation and gene expression in response to HRV infection.
  
  
  CONCLUSIONS
  We describe for the first time that Human rhinovirus infection causes DNA methylation changes in airway epithelial cells that differ between asthmatic and healthy subjects. These epigenetic differences may possibly explain the mechanism by which respiratory viruses cause asthma exacerbations.
authors.forename: Peter
authors.initials: P
authors.lastname: McErlean
authors.forename: Silvio
authors.initials: S
authors.lastname: Favoreto
authors.forename: Fabricio F
authors.initials: FF
authors.lastname: Costa
authors.forename: Junqing
authors.initials: J
authors.lastname: Shen
authors.forename: Jihan
authors.initials: J
authors.lastname: Quraishi
authors.forename: Assel
authors.initials: A
authors.lastname: Biyasheva
authors.forename: Jocelyn J
authors.initials: JJ
authors.lastname: Cooper
authors.forename: Denise M
authors.initials: DM
authors.lastname: Scholtens
authors.forename: Elio F
authors.initials: EF
authors.lastname: Vanin
authors.forename: Maria F
authors.initials: MF
authors.lastname: de Bonaldo
authors.forename: Hehuang
authors.initials: H
authors.lastname: Xie
authors.forename: Marcelo B
authors.initials: MB
authors.lastname: Soares
authors.affiliation: Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. pa@northwestern.edu.
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Avila
mesh_terms: D000328:Adult; D001249:Asthma / Q000235:genetics* / Q000503:physiopathology / Q000821:virology*; D019175:DNA Methylation / Q000235:genetics*; D003710:Demography; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D005260:Female; D005786:Gene Expression Regulation; D056426:Genetic Loci; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008297:Male; D009666:Nose / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010850:Picornaviridae Infections / Q000235:genetics* / Q000473:pathology / Q000821:virology; D025341:Principal Component Analysis; D012129:Respiratory Function Tests; D012229:Rhinovirus / Q000502:physiology*; D055815:Young Adult