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首页> 外文期刊>Trends in Microbiology >Reactivation of latent HIV by histone deacetylase inhibitors
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Reactivation of latent HIV by histone deacetylase inhibitors

机译：通过组蛋白脱乙酰基酶抑制剂重新激活潜在的HIV

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摘要

Latent HIV persists in CD4+ T cells in infected patients under antiretroviral therapy (ART). Latency is associated with transcriptional silencing of the integrated provirus and driven, at least in part, by histone deacetylases (HDACs), a family of chromatin-associated proteins that regulate histone acetylation and the accessibility of DNA to transcription factors. Remarkably, inhibition of HDACs is sufficient to reactivate a fraction of latent HIV in a variety of experimental systems. This basic observation led to the shock and kill idea that forcing the transcriptional activation of HIV might lead to virus expression, to virus- or host-induced cell death of the reactivated cells, and to the eradication of the pool of latently infected cells. Such intervention might possibly lead to a cure for HIV-infected patients. Here, we review the basic biology of HDACs and their inhibitors, the role of HDACs in HIV latency, and recent efforts to use HDAC inhibitors to reactivate latent HIV in vitro and in vivo.
机译：在抗逆转录病毒疗法（ART）的感染患者中，潜在的HIV持续存在于CD4 + T细胞中。延迟与整合的原病毒的转录沉默相关，并且至少部分地受组蛋白脱乙酰基酶（HDACs）的驱动，组蛋白脱乙酰基酶是一种染色质相关蛋白，可调节组蛋白乙酰化和DNA对转录因子的可达性。值得注意的是，在各种实验系统中，抑制HDAC足以重新激活一部分潜伏的HIV。这种基本观察导致震惊和致命的想法，即强迫HIV的转录激活可能导致病毒表达，病毒或宿主诱导的再激活细胞死亡，并消除潜伏感染的细胞。这种干预措施可能会治愈HIV感染者。在这里，我们回顾了HDAC及其抑制剂的基本生物学原理，HDAC在HIV潜伏期中的作用以及最近在体外和体内使用HDAC抑制剂重新激活潜在HIV的努力。

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