The antimicrobial peptide dermaseptin S4 inhibits HIV-1 infectivity in vitro

Abstract

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.

Anti-HIV-1 Activity of Elafin Is More Potent than Its Precursor's, Trappin-2, in Genital Epithelial Cells

“…To evaluate whether Tr and E could interfere with HIV-1 attachment, HEC-1A cells, which are extensively used in the HIV-1 field for their close resemblance to genital ECs (38,58,59), were used. Figure 3A shows that when HIV-1 ADA was pretreated with either Tr or E at a concentration of 1 g/ml, significantly less HIV-1 ADA was captured by HEC-1A cells, as measured by p24 associated with cell lysates.…”

“…Antiviral activities of Tr and E were also evaluated in a transcytosis assay (31,38,59). This assay was used to assess transfer of cell-free HIV-1 across a tight epithelial monolayer of polarized HEC-1A cells (with TER measuring above 350 ⍀/cm 2 ), grown on a semipermeable membrane.…”

Differential Modulation of Human Lactoferrin Activity against Both R5 and X4-HIV-1 Adsorption on Epithelial Cells and Dendritic Cells by Natural Antibodies

“…However, viral membrane is derived from the host cells from which it buds. Thus, the cytotoxicity for host primary cells of a topical microbicide molecule and its effect on the maintenance of the integrity of a tight epithelial cells monolayer are an important issue (7)(8)(9).…”

Antimicrobial peptides: mode of action and perspectives of practical application

“…Так, АМП индолицидин инактивирует ВИЧ-1 вследствие нарушения мембраны вириона [73]. Сходную активность продемонстрировал пептид дермасептин (Dennaseptin) [74]. При этом он не оказывает прямого действия на мембрану ВГП, однако угнетает его адсорбцию на нормальных клетках [75].…”