Human α-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, various host defense mechanisms reduce the adenoviral infectivity and hereby the success of adenoviral transduction. Twenty-eight of 62 BALs from variou...

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Veröffentlicht in:Regulatory peptides 2001-09, Vol.101 (1), p.157-161
Hauptverfasser: Bastian, Andreas, Schäfer, Heiner
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Schäfer, Heiner
description Adenoviral gene transfer is a promising tool for direct treatment of cystic fibrosis by local application of the CFTR-gene via the airway. However, various host defense mechanisms reduce the adenoviral infectivity and hereby the success of adenoviral transduction. Twenty-eight of 62 BALs from various 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 anti-microbial polypeptides called defensins might be involved. Therefore, we investigated the inhibitory potential of the defensins HNP-1 and HBD-2 on adenoviral infectivity. 293 cells infected with adenovirus-type 5 were treated with both peptides. Compared to control, HNP-1 reduced adenoviral infection by more than 95% if administered at 50 μg/ml, and the IC50-value was 15 μg/ml. In contrast, HBD-2 was much less efficient and did not block adenoviral infection at doses up to 50 μg/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 patients with inflammatory diseases.
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subjects Adenoviridae - genetics
alpha-Defensins - pharmacology
Antiviral Agents - analysis
Antiviral Agents - pharmacology
beta-Defensins - pharmacology
Biological and medical sciences
Bronchoalveolar lavage
Bronchoalveolar Lavage Fluid - chemistry
Cystic Fibrosis - therapy
Defense
Dose-Response Relationship, Drug
Gene therapy
Genetic Therapy
Humans
Lung
Lung Diseases - metabolism
Lung Diseases - therapy
Medical sciences
Pneumology
Respiratory system : syndromes and miscellaneous diseases
Transduction, Genetic
Tumor Cells, Cultured
title Human α-defensin 1 (HNP-1) inhibits adenoviral infection in vitro
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