Altering cell death pathways as an approach to cure HIV infection.
Altering cell death pathways as an approach to cure HIV infection.
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DOI：
10.1038/cddis.2013.248
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发表时间：
2013-07-11
影响因子：
9
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中科院分区：
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最近通过骨髓移植结合抑制性抗逆转录病毒疗法(ART)成功控制人类免疫缺陷病毒(HIV)的案例以及很早开始的ART提供了艾滋病毒感染现在可能被治愈的概念的证据。目前专注于基因治疗、增强艾滋病毒特异性免疫、减少炎症和激活潜伏期的努力都是最近优秀评论的主题。我们现在提出了另一个研究HIV治愈的途径：靶向HIV细胞凋亡调控通路。HIV疾病的中心谜团是，HIV感染杀死了它感染的大部分CD4T细胞，但这些幸免的细胞随后成为HIV的潜在储备库，目前的药物对此无效。我们认为，如果能够设计出有利于艾滋病毒感染的所有细胞死亡的策略，或者如果所有释放艾滋病毒的潜伏感染细胞都会屈服于病毒诱导的细胞毒性，那么这些方法与防止传播感染的有效技术相结合，将共同导致艾滋病毒的治愈。这一前提得到了其他病毒系统的观察支持，在这些系统中，生产性感染、细胞凋亡抵抗和潜伏期或持久性的发展之间的关系已经建立。因此，我们认为，重点研究HIV诱导感染细胞凋亡的机制，以及一些细胞如何逃脱生产性HIV感染的促凋亡效应，对于设计新的、合理的治疗HIV感染的方法至关重要。
Recent cases of successful control of human immunodeficiency virus (HIV) by bone marrow transplant in combination with suppressive antiretroviral therapy (ART) and very early initiation of ART have provided proof of concept that HIV infection might now be cured. Current efforts focusing on gene therapy, boosting HIV-specific immunity, reducing inflammation and activation of latency have all been the subject of recent excellent reviews. We now propose an additional avenue of research towards a cure for HIV: targeting HIV apoptosis regulatory pathways. The central enigma of HIV disease is that HIV infection kills most of the CD4 T cells that it infects, but those cells that are spared subsequently become a latent reservoir for HIV against which current medications are ineffective. We propose that if strategies could be devised which would favor the death of all cells which HIV infects, or if all latently infected cells that release HIV would succumb to viral-induced cytotoxicity, then these approaches combined with effective ART to prevent spreading infection, would together result in a cure for HIV. This premise is supported by observations in other viral systems where the relationship between productive infection, apoptosis resistance, and the development of latency or persistence has been established. Therefore we propose that research focused at understanding the mechanisms by which HIV induces apoptosis of infected cells, and ways that some cells escape the pro-apoptotic effects of productive HIV infection are critical to devising novel and rational approaches to cure HIV infection.