DNA Methylation Profiling in Asthmatic and Non Asthmatic Nasal Epithelial Cells During Respiratory Virus Infection

S U N D A Y 487 DNA Methylation Profiling in Asthmatic and Non Asthmatic Nasal Epithelial Cells During Respiratory Virus Infection Peter McErlean, PhD, Silvio Favoreto, Jr, , PhD, Fabricio Costa, PhD, Junquing Shen, PhD, Assel Biyasheva, PhD, Maria de Fatima Bonaldo, PhD, Denise Scholtens, PhD, Hehuang Xie, PhD, Marcelo B. Soares, PhD, Pedro C. Avila, MD, FAAAAI; Northwestern University, Chicago, IL, Childrens Memorial Hospital Research Center, Chicago, IL, Northwestern University Feinberg School of Medicine, Chicago, IL. RATIONALE: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 (n510) and non asthmatic (n510) nasal epithelial cells during respiratory virus infection in vitro. METHODS: Nasal Epithelial cells were obtained adults (60% female, 10% atopic, median age 22.5 yrs) and infected with Human Rhinovirus-16 (MOI52) or medium control for 48hrs. Global and gene specific methylation profiles were determined via Alu element methylation status and Infinium Human Methylation 450 array respectively. RESULTS: Differences in global and gene-specific methylation were identified between groups in both control and infected cultures. Global methylation was significantly increased in asthmatics (p50.04) but decreased in non asthmatics (p50.64) during infection. Changes in gene-specific methylation profiles were most evident during infection for both groups. However a number of immune (CXCR4, HLA-H), cell adhesion (CD47) and cell structure-associated (TUBB2B) genes exhibited significant differential methylation (p5<0.001) between groups during infection. CONCLUSIONS: Our study has identified that respiratory virus infection impacts DNA methylation in nasal epithelial cells. In addition, we have discovered that differential methylation exists between asthmatic and non asthmatics during respiratory virus infection, suggesting the epigenetic mechanisms may play a role in virus-induced asthma exacerbations.