Hepatitis C virus NS5A anchor peptide disrupts human immunodeficiency virus

Hepatitis C virus NS5A anchor peptide disrupts human immunodeficiency virus
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DOI:
10.1073/pnas.0801388105
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发表时间:
2008-04-08
影响因子:
11.1
通讯作者:
Gallay, Philippe A.
Gallay, Philippe A.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Bobardt, Michael D.;Cheng, Guofeng;Gallay, Philippe A.

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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艾滋病毒的传播。在这里,我们报道了一种衍生自丙型肝炎病毒NS 5A锚结构域(在本文中指定为C5 A)的两亲性α-螺旋肽,该肽已被证明对丙型肝炎病毒(HCV)具有杀病毒作用,也对HIV具有有效的抗病毒活性。C5 A对HIV分离株表现出广泛的抗病毒活性,并且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防止HIV的三种体内靶标:CD 4(+)T淋巴细胞、巨噬细胞和树突状细胞的感染。C5 A可以中断正在进行的T细胞感染,并且它可以防止HIV通过原代生殖器上皮细胞的迁移,粘膜靶细胞的感染和从树突状细胞向离体T细胞的转移,证明未来的实验可以确定C5 A是否可以防止HIV在体内传播。
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 a-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.