Research
Inhibition of early steps in the lentiviral replication cycle by cathelicidin host defense peptides
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* Corresponding author: Lars Steinstraesser lars.steinstraesser@ruhr-uni-bochum.de
1 Department for Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Buerkle-de-la- Camp Platz 1, 44789 Bochum, Germany
2 Department of Molecular and Medical Virology, Ruhr University Bochum, Universitätsstraße 150, 44801 Bochum, Germany
3 Department of Dermatology, University Medical Center Nijmegen, Geert Grooteplein 9, 6525 GA Nijmegen, Netherlands
Retrovirology 2005, 2:2 doi:10.1186/1742-4690-2-2
Published: 18 January 2005Abstract
Background
The antibacterial activity of host defense peptides (HDP) is largely mediated by permeabilization of bacterial membranes. The lipid membrane of enveloped viruses might also be a target of antimicrobial peptides. Therefore, we screened a panel of naturally occurring HDPs representing different classes for inhibition of early, Env-independent steps in the HIV replication cycle. A lentiviral vector-based screening assay was used to determine the inhibitory effect of HDPs on early steps in the replication cycle and on cell metabolism.
Results
Human LL37 and porcine Protegrin-1 specifically reduced lentiviral vector infectivity, whereas the reduction of luciferase activities observed at high concentrations of the other HDPs is primarily due to modulation of cellular activity and/ or cytotoxicity rather than antiviral activity. A retroviral vector was inhibited by LL37 and Protegrin-1 to similar extent, while no specific inhibition of adenoviral vector mediated gene transfer was observed. Specific inhibitory effects of Protegrin-1 were confirmed for wild type HIV-1.
Conclusion
Although Protegrin-1 apparently inhibits an early step in the HIV-replication cycle, cytotoxic effects might limit its use as an antiviral agent unless the specificity for the virus can be improved.