Epithelial-mesenchymal transition in paediatric airway epithelial cells following infection with bronchiolitis obliterans associated adenoviruses.

PI: Stephan Stick, MB, Bchir, PhD, MRCHP, FRACP

Institution: Telethon Kids Institute

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Overall goal of the project: Adenoviruses can infect human and certain types (adenovirus 3, 5, 7 and 21) may result in the rare complication post-infectious bronchiolitis obliterans (PI-BO), identified by fibroblastic scarring of the lung. Why this can occur is still poorly understood and as a rare disease, there have been no good models to study the processes involved. Our goal is to investigate how airway cells from young children respond to different adenovirus types. In particular, we are testing whether the PI-BO associated adenovirus types induce a process called epithelial-mesenchymal transition, which can drive fibroblastic scarring.

Outcomes to date: We have obtained and grown adenovirus from clinical samples. The PI-BO associated adenovirus 3 was observed to induce more cytopathic effect (change in cell health) in airway cells than adenovirus 2, which is not associated with PI-BO. Genes involved in epithelial-mesenchymal transition only changed in response to adenovirus 3. We are including other adenovirus types to further drive research into the pathological mechanisms of PI-BO. Overall, this is a promising new laboratory model to assess how the young airway responds to adenovirus.