S U N D A Y 488 Exosomal Mir-155 Secretion during Rhinovirus Infection in EARLY Childhood Maria J. Gutierrez, MD, Giovanny Perez, MD, Krishna Pancham, Shelanoor Huseni, Gustavo Nino, MD; Section of Asthma, Allergy & Immunology, Pennsylvania State University College of Medicine, Hershey, PA, Division of Pediatric Pulmonology and Sleep Medicine, Children’s National Medical Center. RATIONALE: Innate immune responses are fine-tuned by small noncoding RNA molecules termed microRNAs (miRs) that modify gene expression in response to the environment. During acute infections miRs can be secreted in extracellular vesicles (exosomes) to facilitate cell-to-cell genetic communication. In this study we investigated the potential role of exosomal miRs in modulating airway antiviral immunity during rhinovirus (RV) infection, the most common cause of asthma exacerbations in children. METHODS: Nasal airway secretions were obtained from children (<3 yrs old) during PCR-confirmed RV infections and age-matched controls (n520). Nasal exosomes were isolated with polymer-based precipitation (exoquick method) and miRs profiled using NanoString microarrays. Exosomal miRNA results were contrasted with in vitro data from air-liquid interface (ALI)-differentiated human bronchial epithelium (HBE). RESULTS: Nasal exosomal miR profiling identified miR-155 as the top miR present in childrenwith RV (n510) but not in control subjects (n510). Nasal exosomal miR profiling overlapped significantly with exosomal miRs isolated from in vitro HBE secretions indicating an epithelial secretory origin of the isolated nasal exosomes. Through the use of bioinformatics tools, we identified that miR-155 predicted target genes regulate toll-like receptor (TLR)-mediated signaling. CONCLUSIONS: Our data indicate that acute RV infection in young children is associated with airway secretion of exosomes containing miR 155, which is predicted in silico to regulate antiviral immunity. Further characterization of the potential immune regulatory role of virally-induced exosomal miR secretion will enhance our knowledge about the origins of virally-induced asthma and may identify new strategies to treat and monitor this condition in children.