Following reverse transcription, HIV viral DNA is integrated into host cell genomes and establishes a stable latent infection, which has posed a major obstacle for obtaining a cure for HIV. HIV proviral transcription is regulated in cellular reservoirs by complex host epigenetic and transcriptional machineries. The Bromodomain (BD) and Extra-Terminal Domain (ET) protein, BRD4, is an important epigenetic reader that interacts with acetyl-histones and a variety of chromatin and transcriptional regulators to control gene expression, including HIV. Modulation of BRD4 by a pan BET inhibitor (JQ1) has been shown to activate HIV transcription. Recent studies by my group and others indicate that the function of BRD4 is versatile and its effects on HIV transcription may depend on the partner proteins or pathways engaged by BRD4. Our studies have reported a novel class of small-molecule modulators that are distinct from JQ1 but induce HIV transcriptional suppression through BRD4. Herein, we reviewed recent research on the modulation of BRD4 in HIV epigenetic regulation and discussed their potential implications for finding an HIV cure.

中文翻译：

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BRD4 在 HIV 表观遗传调控中的调节：对寻找 HIV 治愈方法的影响

逆转录后，HIV 病毒 DNA 被整合到宿主细胞基因组中，并建立稳定的潜伏感染，这已经成为治愈 HIV 的主要障碍。HIV 前病毒转录在细胞库中由复杂的宿主表观遗传和转录机制调节。Bromodomain (BD) 和 Extra-Terminal Domain (ET) 蛋白 BRD4 是一种重要的表观遗传阅读器，可与乙酰组蛋白和各种染色质和转录调节因子相互作用以控制基因表达，包括 HIV。泛 BET 抑制剂 (JQ1) 对 BRD4 的调节已被证明可以激活 HIV 转录。我的团队和其他人最近的研究表明，BRD4 的功能是多方面的，它对 HIV 转录的影响可能取决于 BRD4 参与的伙伴蛋白或途径。我们的研究报告了一类新的小分子调节剂，它们不同于 JQ1，但通过 BRD4 诱导 HIV 转录抑制。在此，我们回顾了最近在 HIV 表观遗传调控中调节 BRD4 的研究，并讨论了它们对寻找 HIV 治愈方法的潜在影响。