title: Inhibition of early steps in the lentiviral replication cycle by cathelicidin host defense peptides.
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.
  
  
  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.
authors.affiliation: 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
authors.forename: Lars
authors.initials: L
authors.lastname: Steinstraesser
authors.forename: Bettina
authors.initials: B
authors.lastname: Tippler
authors.forename: Janine
authors.initials: J
authors.lastname: Mertens
authors.forename: Evert
authors.initials: E
authors.lastname: Lamme
authors.forename: Heinz-Herbert
authors.initials: HH
authors.lastname: Homann
authors.forename: Marcus
authors.initials: M
authors.lastname: Lehnhardt
authors.forename: Oliver
authors.initials: O
authors.lastname: Wildner
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Steinau
authors.forename: Klaus
authors.initials: K
authors.lastname: Uberla
mesh_terms: 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*
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D010455:Peptides; D011506:Proteins; C466663:novispirin G10; C504857:plectasin; C094880:protegrin-1; D008156:Luciferases