Epithelial defensins impair adenoviral infection: Implication for adenovirus-mediated gene therapy

Epithelial cells have been to participate actively in host defense by produ cing small cationic peptides called defensins, To investigate the biologica l activity of epithelial defensins in more detail, we expressed two defensi ns, hBD-1 and HD-5, in eukaryotic cell lines. Defensins were localized in t he cytoplasm and in cell culture medium and exhibited strong microbicidal a ctivity toward Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Moreover, our data indicate that the presence of defensins protect ed the cells from adenoviral infection. The presence of HD-5 or hBD-1 reduc ed the infectivity of Av1Cf2 three- to fivefold. These results imply that d efensins must be considered a serious obstacle whenever adenovirus is used to deliver genes to epithelial cells.