Novel anti-HIV therapeutics targeting chemokine receptors and actin regulatory pathways.
Novel anti-HIV therapeutics targeting chemokine receptors and actin regulatory pathways.
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DOI：
10.1111/imr.12106
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发表时间：
2013-11
影响因子：
8.7
通讯作者：
Wu Y
中科院分区：
文献类型：
--
作者：
Spear M;Guo J;Wu Y
人类免疫缺陷病毒-1（HIV-1）感染辅助性CD 4 + T细胞，并导致CD 4 + T细胞耗竭和免疫缺陷。在过去30年中，抗逆转录病毒疗法取得了重大进展，这一疾病已经可以控制。尽管如此，有效的疫苗仍然遥遥无期，治愈或功能性治愈还有待发现。在可能的治愈性疗法中，主要针对病毒蛋白的传统抗逆转录病毒疗法已被证明无效。靶向HIV依赖性宿主辅因子可能提供替代方案，既可预防HIV传播，又可阻止疾病进展。最近，血液CD 4 + T细胞中的肌动蛋白细胞骨架及其调节因子已成为可以靶向的主要宿主辅因子。皮质肌动蛋白是病毒进入和早期进入后迁移的屏障，这一新概念导致了皮质肌动蛋白层病毒-宿主相互作用的新生模型。破译细胞调控途径已经为未来的治疗展示了令人兴奋的前景。在这篇综述中，我们描述了艾滋病毒与肌动蛋白细胞骨架的相互作用的研究。我们还研究了从这种相互作用中出现的潜在药理学靶点。此外，我们简要讨论了几个肌动蛋白途径为基础的抗艾滋病毒药物，目前正在开发或测试。
The human immunodeficiency virus-1 (HIV-1) infects helper CD4+ T cells, and causes CD4+ T-cell depletion and immunodeficiency. In the past 30 years, significant progress has been made in antiretroviral therapy, and the disease has become manageable. Nevertheless, an effective vaccine is still nowhere in sight, and a cure or a functional cure awaits discovery. Among possible curative therapies, traditional antiretroviral therapy, mostly targeting viral proteins, has been proven ineffective. It is possible that targeting HIV-dependent host cofactors may offer alternatives, both for preventing HIV transmission and for forestalling disease progression. Recently, the actin cytoskeleton and its regulators in blood CD4+ T cells have emerged as major host cofactors that could be targeted. The novel concept that the cortical actin is a barrier to viral entry and early post-entry migration has led to the nascent model of virus-host interaction at the cortical actin layer. Deciphering the cellular regulatory pathways has manifested exciting prospects for future therapeutics. In this review, we describe the study of HIV interactions with actin cytoskeleton. We also examine potential pharmacological targets that emerge from this interaction. In addition, we briefly discuss several actin pathway-based anti-HIV drugs that are currently in development or testing.
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