The antimicrobial peptide dermaseptin S4 inhibits HIV-1 infectivity in vitro.
Most of HIV-1 infections are acquired through sexual contact. In the absence of a preventive vaccine, the development of topical microbicides that can block infection at the mucosal tissues is needed. Dermaseptin S4 (DS4) is an antimicrobial peptide derived from amphibian skin, which displays a broad spectrum of activity against bacteria, yeast, filamentous fungi, and herpes simplex virus type 1. We show here that DS4 inhibits cell-free and cell-associated HIV-1 infection of P4-CCR5 indicator cells and human primary T lymphocytes. The peptide is effective against R5 and X4 primary isolates and laboratory-adapted strains of HIV-1. Its activity is directed against HIV-1 particles by disrupting the virion integrity. Increasing the number of DS4-positive charges reduced cytotoxicity without affecting the antiviral activity. The modified DS4 inhibited HIV-1 capture by dendritic cells and subsequent transmission to CD4(+) T cells, as well as HIV-1 binding on HEC-1 endometrial cells and transcytosis through a tight epithelial monolayer.
Lorin
Clarisse
C
Unité des Virus Lents, CNRS URA 1930, Institut Pasteur, 28 rue du Dr Roux, 75015 Paris, France.
Saidi
Héla
H
Belaid
Afifa
A
Zairi
Amira
A
Baleux
Françoise
F
Hocini
Hakim
H
Bélec
Laurent
L
Hani
Khaled
K
Tangy
Frédéric
F
D029845:Amphibian Proteins / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000821:virology; D004847:Epithelial Cells / Q000821:virology; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity*; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D009000:Monocytes / Q000821:virology; D019713:Receptors, CCR5 / Q000378:metabolism; D013601:T-Lymphocytes / Q000821:virology; D014771:Virion / Q000187:drug effects / Q000378:metabolism
D029845:Amphibian Proteins; D023181:Antimicrobial Cationic Peptides; D019713:Receptors, CCR5; C109653:dermaseptin 4 protein, Phyllomedusa