Human alpha-defensin 1 (HNP-1) inhibits adenoviral infection in vitro

Adenoviral gene transfer is a promising tool for direct treatment of cystic fibrosis by local application of the CFTR-gene via the airway. However, va rious host defense mechanisms reduce the adenoviral infectivity and hereby the success of adenoviral transduction. Twenty-eight of 62 BALs from variou s patients exerted strong inhibition of adenoviral infection of 293 cells. This soluble activity could be attributed to larger peptides rather than to small molecules. Beside immunoglobulins, certain epithelial cell-derived a nti-microbial polypeptides called defensins might be involved. Therefore, w e investigated the inhibitory potential of the defensins HNP-1 and HBD-2 on adenoviral infectivity. 293 cells infected with adenovirus-type 5 were tre ated with both peptides. Compared to control, HNP-1 reduced adenoviral infe ction by more than 95% if administered at 50 mug/ml, and the IC50-value was 15 mug/ml. In contrast, HBD-2 was much less efficient and did not block ad enoviral infection at doses up to 50 mug/ml. Our data demonstrate that the presence of certain polypeptides in the BAL, i.e. the defensin HNP-1, might be the major obstacle for adenoviral gene transfer, particularly in patien ts with inflammatory diseases. (C) 2001 Elsevier Science B.V. All rights re served.