Grant: Project Grant

Asthma is a chronic airway disease that affects 300 million people worldwide. Although all children get multiple infections with human rhinovirus (HRV - the "common cold virus") in early life, only a subset get HRV-induced wheezing illnesses, and are far more likely to develop asthma by age 6. It is not clear why only some children get HRV-induced wheezing illnesses, but the interaction of HRV and development of allergies may play a role. Human airway epithelial cells (HAE) are the main site of HRV infection and it is thought that HRV affects asthma by changing HAE biology. The characteristic features (phenotype) of HAE are altered in asthma, and these altered HAE interact with nearby structural and immune cells to help cause asthma. Despite the central role of HAE in regulating airway diseases, the effects of HRV infection on HAE phenotype have not been well characterized. We have found that HRV infection of HAE from normal people causes transient changes in cell biology. In this proposal, we will fully characterize the effects of HRV on epithelial phenotype and will define the mechanisms by which HRV causes these changes. We will determine if repeated infections with HRV cause greater effects in HAE than a single infection. In addition, we will test the idea that HRV infections (single or repeated) in the setting of an "allergic" environment produce more profound alterations in HAE that mimic the phenotype seen in asthma. We will compare HAE from asthmatic children to those from normal children to see if they have greater responses to HRV. Finally, we will experimentally infect normal and asthmatic volunteers with HRV to test the idea that HAE in asthmatic patients show greater response to HRV in vivo. By understanding how HRV infections alter epithelial responses, alone and in an allergic setting, we may be able to develop ways to prevent or reduce the effects of HRV in asthma in order to improve the well-being of patients with asthma.