MRC-GSK Alliance: Mechanisms of interplay between allergy and viruses in asthma

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We apply to form an Alliance between GSK and the MRC & Asthma UK Centre in Allergic Mechanisms of Asthma to discover and develop new approaches for prevention/treatment of asthma and asthma attacks. We will integrate research in areas of major strength for the Centre with the strengths in asthma drug discovery at GSK. The overall aim is to investigate mechanisms of interplay between allergy and virus infection in development of asthma and in acute asthma attacks. The major cause of asthma attacks are human rhinovirus (RV) infections, these are also related to development of asthma when they occur in early life. We will investigate gene expression and how expression is regulated in lung cells during RV infection to identify molecules/pathways induced by RV infection that are implicated in promoting allergic responses.We will determine whether RV induction/modification of these molecules/processes are related to pre-existing allergic responses, virus load and clinical severity of asthma exacerbation. A major cause of asthma is failure of development of immunological tolerance to allergens. We have shown that tolerance can be reversed by a virus infection, but the mechanisms are unknown. We will purify lung cells from the virus-induced breakdown of tolerance model to identify genes implicated in tolerance breakdown and determine whether these are replicated in lung cells in the human.Finally we will determine whether blocking or inducing molecules implicated in virus induced worsening of allergic responses/breakdown of tolerance, determines severity of RV induced allergic airway inflammation.Accomplishment of these aims will identify targets for development of novel therapies for asthma and asthma attacks.