HIV 潜伏逆转中的异构体选择性与非选择性组蛋白去乙酰化酶抑制剂。
Isoform-Selective Versus Nonselective Histone Deacetylase Inhibitors in HIV Latency Reversal.
机构信息
Department of Virology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana.
Departments of Medicine and Molecular Microbiology, Washington University in St. Louis, St. Louis, Missouri, USA.
出版信息
AIDS Res Hum Retroviruses. 2022 Aug;38(8):615-621. doi: 10.1089/AID.2021.0195.
HIV remains incurable due to the persistence of a latent viral reservoir found in HIV-infected cells, primarily resting memory CD4 T cells. Depletion of this reservoir may be the only way to end this deadly epidemic. In latency, the integrated proviral DNA of HIV is transcriptionally silenced partly due to the activity of histone deacetylases (HDACs). One strategy proposed to overcome this challenge is the use of HDAC inhibitors (HDACis) as latency reversal agents to induce viral expression (shock) under the cover of antiretroviral therapy. It is hoped that this will lead to elimination of the reservoir by immunologic and viral cytopathic (kill). However, there are 18 isoforms of HDACs leading to varying selectivity for HDACis. In this study, we review HDACis with emphasis on their selectivity for HIV latency reversal.
由于潜伏在 HIV 感染细胞中的病毒库（主要是静息记忆 CD4 T 细胞）的存在，HIV 仍然无法治愈。清除这个病毒库可能是结束这种致命传染病的唯一方法。在潜伏状态下，HIV 的整合前病毒 DNA 由于组蛋白去乙酰化酶（HDACs）的活性而部分转录沉默。克服这一挑战的一种策略是使用 HDAC 抑制剂（HDACi）作为潜伏逆转剂，在抗逆转录病毒治疗的掩盖下诱导病毒表达（休克）。人们希望这将通过免疫和病毒细胞病变（杀伤）来消除病毒库。然而，HDAC 有 18 种同工酶，导致 HDACi 的选择性不同。在这项研究中，我们重点回顾了 HDACi 及其对 HIV 潜伏逆转的选择性。
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