Combination antiretroviral therapy (cART) has significantly reduced the mortality rate and morbidity, and has increased the life expectancy of the human immunodeficiency virus (HIV) infected patients. However, the current cART is incapable of eradicating viruses from the human body, and HIV remains one of the most notorious viruses mankind has ever faced. HIV-1 enters target cells through the binding of gp120 viral protein to a CD4 receptor and then to a coreceptor, C-C chemokine receptor 5 (CCR5) or C-X-C chemokine receptor type 4 (CXCR4). Individuals homozygous for a 32-bp deletion in the CCR5 allele, CCR5Δ32, are almost completely resistant to HIV-1 acquisition. Moreover, several of natural CXCR4 mutants which have been identified can reduce HIV-1 entry without impairing either ligand binding or signaling. In order to get rid of indefinite treatment for HIV patients, there is a growing interest in creating an HIV-resistant immune system through the use of CCR5 and CXCR4-modified hematopoietic stem cells (HSCs). Proof of concept for this approach has been provided in the instance of "Berlin patient" transplanted with allogeneic stem cells from a donor with homozygosity for the CCR5Δ32 deletion. Here, we review the progress of coreceptor-based HSC gene therapy for HIV disease and present new strategies.

中文翻译：

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基于Coreceptor的造血干细胞基因治疗HIV疾病。

联合抗逆转录病毒疗法（cART）大大降低了死亡率和发病率，并提高了人类免疫缺陷病毒（HIV）感染患者的预期寿命。但是，当前的cART无法消除人体中的病毒，而HIV仍然是人类有史以来最臭名昭著的病毒之一。HIV-1通过gp120病毒蛋白与CD4受体，然后与共受体CC趋化因子受体5（CCR5）或CXC趋化因子受体4型（CXCR4）的结合进入靶细胞。CCR5等位基因CCR5Δ32中32 bp缺失纯合的个体几乎完全抗HIV-1感染。此外，已鉴定的几种天然CXCR4突变体可以减少HIV-1的进入，而不会损害配体结合或信号传导。为了摆脱对HIV患者的无限期治疗，人们越来越有兴趣通过使用CCR5和CXCR4修饰的造血干细胞（HSC）创建抗HIV的免疫系统。在“柏林患者”的情况下提供了这种方法的概念证明，该患者移植了来自供体的同种异体干细胞，具有CCR5Δ32缺失的纯合性。在这里，我们回顾了基于共同受体的HSC基因治疗HIV疾病的进展，并提出了新的策略。将来自供体的同种异体干细胞移植到CCR5Δ32缺失的纯合子上。在这里，我们回顾了基于共同受体的HSC基因治疗HIV疾病的进展，并提出了新的策略。将来自供体的同种异体干细胞移植到CCR5Δ32缺失的纯合子上。在这里，我们回顾了基于共同受体的HSC基因治疗HIV疾病的进展，并提出了新的策略。