Inhibition of Early Steps in the Lentiviral Replication Cycle by Cathelicidin Host Defense Peptides

Overview

Journal Retrovirology

Publisher Biomed Central

Specialty Microbiology

Date 2005 Jan 20

PMID 15656908

Citations 45

Authors

Lars Steinstraesser

Bettina Tippler

Janine Mertens

Evert Lamme

Heinz-Herbert Homann

Marcus Lehnhardt

Oliver Wildner

Hans-Ulrich Steinau

Klaus Uberla

Affiliations

Soon will be listed here.

Abstract

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.

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