Lorin Clarisse, Saidi Héla, Belaid Afifa, Zairi Amira, Baleux Françoise, Hocini Hakim, Bélec Laurent, Hani Khaled, Tangy Frédéric
Unité des Virus Lents, CNRS URA 1930, Institut Pasteur, 28 rue du Dr Roux, 75015 Paris, France.
Virology. 2005 Apr 10;334(2):264-75. doi: 10.1016/j.virol.2005.02.002.
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.
大多数HIV-1感染是通过性接触获得的。在缺乏预防性疫苗的情况下，需要开发能够在黏膜组织阻断感染的局部用杀微生物剂。皮肤防御素S4（DS4）是一种源自两栖动物皮肤的抗菌肽，对细菌、酵母、丝状真菌和1型单纯疱疹病毒具有广泛的活性。我们在此表明，DS4可抑制P4-CCR5指示细胞和人原代T淋巴细胞的无细胞和细胞相关HIV-1感染。该肽对R5和X4原代分离株以及实验室适应的HIV-1毒株有效。其活性通过破坏病毒体完整性针对HIV-1颗粒。增加DS4的正电荷数量可降低细胞毒性，而不影响抗病毒活性。修饰后的DS4抑制树突状细胞捕获HIV-1并随后传播至CD4(+) T细胞，以及HIV-1在HEC-1子宫内膜细胞上的结合和通过紧密上皮单层的转胞吞作用。
