Specific reactivation of latent HIV-1 with designer zinc-finger transcription factors targeting the HIV-1 5′-LTR promoter
Specific reactivation of latent HIV-1 with designer zinc-finger transcription factors targeting the HIV-1 5′-LTR promoter
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DOI：
10.1038/gt.2014.21
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发表时间：
2014-03
期刊：
影响因子：
5.1
通讯作者：
Pengfei Wang;Xiying Qu;Xiaoying Wang;X. Zhu;Hanxian Zeng;Huabiao Chen;Huanzhang Zhu
中科院分区：
文献类型：
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作者：
Pengfei Wang;Xiying Qu;Xiaoying Wang;X. Zhu;Hanxian Zeng;Huabiao Chen;Huanzhang Zhu
HIV-1 潜伏期仍然是根除该病毒的主要障碍。目前的潜伏期逆转剂不能有效、特异性地消除潜伏的 HIV-1 病毒库。因此，迫切需要更好的方法。在这项研究中，我们描述了一种利用由设计锌指蛋白和转录激活结构域 VP64 组成的锌指转录因子重新激活潜伏 HIV-1 的新策略。我们首次证明，具有 HIV-1 长末端重复（LTR）启动子特异性亲和力的 ZF-VP64 可以显着重新激活潜伏感染细胞中的 HIV-1 表达，而不改变细胞增殖或细胞周期进程。我们还提供证据表明，ZF-VP64 通过与 5'-LTR 启动子特异性结合来重新激活 HIV-1。我们的结果证明了这种新方法用于抗 HIV-1 潜伏疗法的潜力。
HIV-1 latency remains the primary obstacle to the eradication of this virus. The current latency-reversing agents cannot effectively and specifically eliminate latent HIV-1 reservoirs. Therefore, better approaches are urgently needed. In this study, we describe a novel strategy to reactivate latent HIV-1 using zinc-finger transcription factors composed of designer zinc-finger proteins and the transcriptional activation domain VP64. For the first time, we demonstrate that ZF-VP64 with HIV-1 long terminal repeat (LTR) promoter-specific affinity could significantly reactivate HIV-1 expression from latently infected cells without altering cell proliferation or cell cycle progression. We also provide evidence that the reactivation of HIV-1 by ZF-VP64 occurs through specific binding to the 5′-LTR promoter. Our results demonstrate the potential of this novel approach for anti-HIV-1 latency therapy.