Pöhlmann Stefan, Reeves Jacqueline D
Institute for Clinical and molecular Virology and Nikolaus-Fiebiger-Center for Molecular Medicine, University Erlangen-Nürnberg, Erlangen, Germany.
Curr Pharm Des. 2006;12(16):1963-73. doi: 10.2174/138161206777442155.
In the absence of a vaccine which could stop the HIV/AIDS pandemic, the development of therapeutic options is of utmost interest. The combined use of inhibitors of reverse transcriptase and protease as highly active antiretroviral therapy (HAART) provided the first effective treatment of HIV/AIDS and significantly decreased the number of AIDS related deaths in industrialized countries. However, the emergence of resistant viruses and the toxic side effects of HAART highlights that novel therapies are urgently required. The inhibition of HIV-1 entry is a promising option. Entry of HIV-1 into target cells involves interactions of the viral envelope protein (Env) with CD4 and a coreceptor, usually CCR5 or CXCR4. Env binding to receptor triggers several conformational rearrangements in Env, which involve the creation and/or exposure of structural intermediates pivotal to fusion of the viral and cellular membranes. Both, cellular receptors and structures in Env associated with membrane fusion are targets for therapeutic intervention. Here, we will discuss how HIV-1 enters cells and introduce strategies how this process can be inhibited.
在缺乏能够阻止艾滋病毒/艾滋病大流行的疫苗的情况下，开发治疗方案至关重要。逆转录酶抑制剂和蛋白酶抑制剂联合使用作为高效抗逆转录病毒疗法（HAART），首次实现了对艾滋病毒/艾滋病的有效治疗，并显著降低了工业化国家与艾滋病相关的死亡人数。然而，耐药病毒的出现以及HAART的毒副作用凸显出迫切需要新的疗法。抑制HIV-1进入是一个有前景的选择。HIV-1进入靶细胞涉及病毒包膜蛋白（Env）与CD4和一种共受体（通常是CCR5或CXCR4）的相互作用。Env与受体的结合会引发Env中的几种构象重排，这涉及到对病毒和细胞膜融合至关重要的结构中间体的产生和/或暴露。细胞受体和Env中与膜融合相关的结构都是治疗干预的靶点。在此，我们将讨论HIV-1如何进入细胞，并介绍抑制这一过程的策略。
