Novel approaches to inhibit HIV entry.

Novel approaches to inhibit HIV entry.
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DOI:
10.3390/v4020309
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发表时间:
2012-02
期刊:
Viruses
影响因子:
--
通讯作者:
Doms RW
Doms RW
中科院分区:
其他
文献类型:
--
作者:
Didigu CA;Doms RW

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人类免疫缺陷病毒(HIV)进入靶细胞是一个多步骤的过程,涉及病毒糖蛋白Env与其受体CD 4和辅助受体CCR 5或CXCR 4的结合。了解HIV进入细胞的方式导致了对遗传多态性的鉴定,例如ccr 5基因中的32个碱基对缺失(ccr 5 → 32)赋予纯合个体对感染的抵抗力,并且还导致了在进入步骤阻断感染的进入通道-小分子拮抗剂的开发。最近证明了使用来自ccr 5纯合供体的细胞进行造血干细胞移植后白血病患者中HIV感染的长期控制,突出了HIV进入在维持已建立的感染中的重要作用,并导致了通过遗传修饰ccr 5基因来治疗HIV感染的许多尝试。在这篇综述中,我们描述了HIV进入过程,并提供了不同类别的批准HIV进入抑制剂的概述,同时强调了新的遗传策略,旨在阻止HIV感染的入境水平。
Human Immunodeficiency Virus (HIV) entry into target cells is a multi-step process involving binding of the viral glycoprotein, Env, to its receptor CD4 and a coreceptor—either CCR5 or CXCR4. Understanding the means by which HIV enters cells has led to the identification of genetic polymorphisms, such as the 32 base-pair deletion in the ccr5 gene (ccr5∆32) that confers resistance to infection in homozygous individuals, and has also resulted in the development of entry inhibitors—small molecule antagonists that block infection at the entry step. The recent demonstration of long-term control of HIV infection in a leukemic patient following a hematopoietic stem cell transplant using cells from a ccr5∆32 homozygous donor highlights the important role of the HIV entry in maintaining an established infection and has led to a number of attempts to treat HIV infection by genetically modifying the ccr5 gene. In this review, we describe the HIV entry process and provide an overview of the different classes of approved HIV entry inhibitors while highlighting novel genetic strategies aimed at blocking HIV infection at the level of entry.
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