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Address: 240 EMRB
Phone: (319) 335-6933
Mentor: Paul McCray, MD
Undergraduate Institution: University of Nebraska - Lincoln
Cystic fibrosis (CF) is an autosomal recessive disorder characterized by progressive lung disease as well as pancreas, liver, and intestinal dysfunction. While bacterial colonization of the lungs has been well studied in CF, the impact of viral infections on the progression of the disease is under appreciated. There is growing evidence that infants and children with CF have more severe viral infections compared to non-CF children. Additionally, it has been shown that certain viruses replicate more readily in CF airway cells. These viral infections may contribute to the onset and progression of CF lung disease, including pulmonary exacerbations and bacterial colonization. One possible reason for the difference in viral infection in CF and non-CF patients may have to do with the antimicrobial properties of airway surface liquid (ASL). ASL-derived antimicrobials form an important line of defense against respiratory pathogens. Previous studies using a porcine model of CF showed that ASL contains a number of components that act synergistically to rapidly kill or inactivate bacterial pathogens in a pH-dependent manner, and that this antibacterial activity is impaired in CF ASL relative to non-CF ASL. However, it has yet to be determined whether ASL also possesses an analogous system for inactivation of respiratory viruses. We hypothesize that ASL does possess antiviral activity that differs between CF and non-CF subjects. To test these hypotheses, we developed a viral inactivation assay with which to characterize the antiviral properties of ASL from CF and non-CF individuals and animals.
So far we have determined that porcine tracheal ASL has antiviral activity and that nasal secretions from newborn CF pigs have reduced antiviral activity compared to nasal secretions from their non-CF littermates. We wish to further characterize the antiviral properties of ASL by identifying some of the key players. We also hope to determine why ASL from CF pigs has less antiviral activity compared to non-CF ASL.
Berkebile AR and McCray Jr PB. Impact of airway surface liquid pH on host defensein cystic fibrosis. Int J Biochem Cell Biol. 2014. 52: 124-129.
Derscheid RJ, van Geelen A, Berkebile AR, Gallup JM, Hostetter SJ, Banfi B, McCray Jr PB, Ackermann MR. Increased Concentration of Iodide in Airway Secretions is Associated With Reduced RSV Disease Severity. Am J Respir Cell Mol Biol. 2013. 50:389-97.
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