Designed transcription activator-like effector proteins efficiently induced the expression of latent HIV-1 in latently infected cells.
Designed transcription activator-like effector proteins efficiently induced the expression of latent HIV-1 in latently infected cells.
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DOI：
10.1089/aid.2014.0121
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发表时间：
2015-01
影响因子：
1.5
通讯作者：
Xiaohui Wang;Pengfei Wang;Z. Fu;Haiyan Ji;Xiying Qu;Hanxian Zeng;Xiaoli Zhu;Junxiao Deng;
中科院分区：
文献类型：
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作者：
Xiaohui Wang;Pengfei Wang;Z. Fu;Haiyan Ji;Xiying Qu;Hanxian Zeng;Xiaoli Zhu;Junxiao Deng;
HIV潜伏期是清除患者体内HIV感染的最大障碍。重新激活潜伏的 HIV-1 是消除这些病毒库的一种有前景的策略。在这里，我们报告了一种重新激活潜伏的 HIV-1 原病毒的新方法，使用人工设计的转录激活因子样效应器 (TALE) 融合蛋白，该融合蛋白包含专门针对 HIV-1 启动子和基于单纯疱疹病毒的转录激活因子 VP64 结构域的 DNA 结合域。我们设计了四个编码 TALE 蛋白的 TALE 基因 (TALE1-4)，每个基因专门针对 HIV-1 启动子内不同的 20 bp DNA 序列，并构建了四个对应于 TALE1-4 的 TALE-VP64 表达载体。我们发现 TALE1-VP64 有效地重新激活了潜伏感染的 C11 和 A10.6 细胞中的 HIV-1 基因表达。我们进一步证实 TALE1-VP64 通过与 HIV-LTR 启动子特异性结合来重新激活潜在的 HIV-1。此外，我们还发现TALE1-VP64不影响细胞增殖或细胞周期分布。总而言之，我们的数据表明 TALE1-VP64 可以特异性、有效地重新激活潜伏的 HIV-1 转录，表明该策略可能为未来的抗 HIV-1 潜伏治疗提供一种新方法。
HIV latency is the foremost barrier to clearing HIV infection from patients. Reactivation of latent HIV-1 represents a promising strategy to deplete these viral reservoirs. Here, we report a novel approach to reactivate latent HIV-1 provirus using artificially designed transcription activator-like effector (TALE) fusion proteins containing a DNA-binding domain specifically targeting the HIV-1 promoter and the herpes simplex virus-based transcriptional activator VP64 domain. We engineered four TALE genes (TALE1-4) encoding TALE proteins, each specifically targeting different 20-bp DNA sequences within the HIV-1 promoter, and we constructed four TALE-VP64 expression vectors corresponding to TALE1-4. We found that TALE1-VP64 effectively reactivated HIV-1 gene expression in latently infected C11 and A10.6 cells. We further confirmed that TALE1-VP64 reactivated latent HIV-1 via specific binding to the HIV-LTR promoter. Moreover, we also found that TALE1-VP64 did not affect cell proliferation or cell cycle distribution. Taken together, our data demonstrated that TALE1-VP64 can specifically and effectively reactivate latent HIV-1 transcription, suggesting that this strategy may provide a novel approach for anti-HIV-1 latency therapy in the future.