Oral Presentation 9th Australasian Virology Society Meeting 2017

Viral exacerbation of asthma (#13)

Nathan Bartlett 1
  1. University of Newcastle, CALLAGHAN, NSW, Australia

Human rhinoviruses are responsible for more infections in humans than any other clinically important virus and familiar to all of us as the cause of the common cold. Over 150 genetically/antigenically distinct subtypes belonging to 3 species have been identified with any number of these circulating within the population at any given time. Whilst many rhinovirus infections are asymptomatic, or cause mild upper respiratory tract illness (cold) they are also capable of progressing to the lower respiratory tract where a complex interaction with the host occurs that can trigger an exacerbation of chronic respiratory diseases such as asthma and COPD. Indeed rhinoviruses are now recognized to be the most clinically significant respiratory virus as a result of their predominant role in triggering acute exacerbations of chronic respiratory diseases. My research has focused on the host response to rhinovirus infection initiated by airway epithelium. Using a combination of human experimental rhinovirus infection, ex vivo cultured primary human bronchial epithelial cells and mouse models we have identified that in asthma this response is dysregulated, characterised by deficient interferon production and over-expression of type -2 immune activating cytokines such as IL-25. Mechanisms driving this include an intrinsic defect in the epithelial innate anti-viral immune response which is potentially linked to autocrine negative regulation by IL-25. We have also discovered that deficient anti-viral immunity is compounded by mechanical forces generated by bronchoconstriction, which is the hallmark pathophysiological response in asthma. By understanding the complex interplay between rhinovirus and host that plays out at the respiratory epithelium we able to develop treatments that prevent viral activation of the immune pathways that exacerbate inflammatory airways diseases.