Viral respiratory infections have important roles in inception and exacerbation of asthma. The goal of this AADRC is to determine the mechanisms by which respiratory viruses contribute to the pathogenesis of asthma. The Virology Core is established to provide uniform stocks of respiratory viruses and related materials for each of the five projects. To accomplish this goal, stock preparations of human RV strains will be prepared for Projects 1, 3, 4, and 5. For Project 1, the Core will use the prepared human RV16 for inoculation of selected study subjects and confirm the presence of RV16 by culture and RT-PCR. In addition, the Core will continue to prepare monoclonal antibodies against RV16 and C3 convertase; these antibodies will be used to analyze, by immunohistochemical techniques, the presence of RV in airway tissues from experimentally and naturally infected subjects. Project 2 has developed an animal model for asthma: the Sendai-virus-infected Brown Norway weanling rat. The Virology Core will provide and inoculate these animals with Sendai virus and confirm infection by culture. Project 3 is designed to determine the signal transduction pathways of human monocytes/macrophages following activation by RV; the Core will provide this virus and establish infection in these cells when necessary. Project 4 is designed to determine the mechanisms of epithelial cell generation of IL-8 following activation with RV. The Core will provide the cultured primary human epithelial cells and RV for these experiments. Finally, Project 5 will determine the effect of RV-generated inflammatory factors, particularly IL-8, on neutrophil adhesion and migration; the Core will provide RV for these experiments.
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