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


CONCLUSIONS
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.
Steinstraesser
Lars
L
Department for Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Buerkle-de-la- Camp Platz 1, 44789 Bochum, Germany. lars.steinstraesser@ruhr-uni-bochum.de
Tippler
Bettina
B
Mertens
Janine
J
Lamme
Evert
E
Homann
Heinz-Herbert
HH
Lehnhardt
Marcus
M
Wildner
Oliver
O
Steinau
Hans-Ulrich
HU
Uberla
Klaus
K
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000633:toxicity; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology* / Q000633:toxicity; D054804:Cathelicidins; D002460:Cell Line; D005822:Genetic Vectors; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D006095:Gram-Positive Cocci / Q000187:drug effects / Q000254:growth & development; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016086:Lentivirus / Q000187:drug effects* / Q000502:physiology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology / Q000633:toxicity; D011506:Proteins / Q000494:pharmacology* / Q000633:toxicity; D014161:Transduction, Genetic; D014779:Virus Replication / Q000187:drug effects*
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D010455:Peptides; D011506:Proteins; C466663:novispirin G10; C504857:plectasin; C094880:protegrin-1; D008156:Luciferases