Bobardt Michael D, Cheng Guofeng, de Witte Lot, Selvarajah Suganya, Chatterji Udayan, Sanders-Beer Brigitte E, Geijtenbeek Teunis B H, Chisari Francis V, Gallay Philippe A
Departments of Immunology and Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5525-30. doi: 10.1073/pnas.0801388105. Epub 2008 Mar 31.
In the absence of an effective vaccine, there is an urgent need for safe and effective antiviral agents to prevent transmission of HIV. Here, we report that an amphipathic alpha-helical peptide derived from the hepatitis C virus NS5A anchor domain (designated C5A in this article) that has been shown to be virocidal for the hepatitis C virus (HCV) also has potent antiviral activity against HIV. C5A exhibits a broad range of antiviral activity against HIV isolates, and it prevents infection of the three in vivo targets of HIV: CD4(+) T lymphocytes, macrophages, and dendritic cells by disrupting the integrity of the viral membrane and capsid core while preserving the integrity of host membranes. C5A can interrupt an ongoing T cell infection, and it can prevent transmigration of HIV through primary genital epithelial cells, infection of mucosal target cells and transfer from dendritic cells to T cells ex vivo, justifying future experiments to determine whether C5A can prevent HIV transmission in vivo.
在缺乏有效疫苗的情况下，迫切需要安全有效的抗病毒药物来预防HIV传播。在此，我们报告一种源自丙型肝炎病毒NS5A锚定结构域的两亲性α-螺旋肽（本文中命名为C5A），该肽已被证明对丙型肝炎病毒（HCV）具有杀病毒活性，对HIV也具有强大的抗病毒活性。C5A对HIV分离株表现出广泛的抗病毒活性，它通过破坏病毒膜和衣壳核心的完整性，同时保持宿主膜的完整性，来预防HIV在体内的三个靶标：CD4(+) T淋巴细胞、巨噬细胞和树突状细胞的感染。C5A可以中断正在进行的T细胞感染，并且可以防止HIV通过原发性生殖上皮细胞的迁移、黏膜靶细胞的感染以及离体状态下从树突状细胞向T细胞的转移，这为未来确定C5A是否能在体内预防HIV传播的实验提供了依据。
