Inhibition of early steps in the lentiviral replication cycle by cathelicidin host defense peptides

• Main Authors: Wildner Oliver, Lehnhardt Marcus, Homann Heinz-Herbert, Lamme Evert, Mertens Janine, Tippler Bettina, Steinstraesser Lars, Steinau Hans-Ulrich, Überla Klaus
• Format: Article
• Language: English
• Published: BMC 2005-01-01
• Series: Retrovirology
• Online Access: http://www.retrovirology.com/content/2/1/2

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>