Specific and Stable Suppression of HIV Provirus Expression In Vitro by Chimeric Zinc Finger DNA Methyltransferase 1.
Specific and Stable Suppression of HIV Provirus Expression In Vitro by Chimeric Zinc Finger DNA Methyltransferase 1.
复制标题
嵌合锌指 DNA 甲基转移酶 1 特异性、稳定地抑制 HIV 原病毒体外表达
DOI：
10.1016/j.omtn.2017.01.002
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发表时间：
2017-03-17
期刊：
影响因子：
--
通讯作者：
Zhu H
中科院分区：
文献类型：
--
作者：
Deng J;Qu X;Lu P;Yang X;Zhu Y;Ji H;Wang Y;Jiang Z;Li X;Zhong Y;Yang H;Pan H;Young WB;Zhu H
HIV-1将其前病毒DNA插入感染的宿主细胞中，然后HIV前病毒DNA可以随着每次细胞分裂而沿着复制。因此，目前的抗逆转录病毒疗法不能完全根除前病毒。我们已经开发出一种创新的策略，通过靶向HIV启动子区域的DNA甲基化来沉默HIV前病毒。我们基因工程嵌合DNA甲基转移酶1组成的设计锌指蛋白，成为ZF 2 DNMT 1。将编码该嵌合蛋白的分子克隆瞬时转染入HIV-1感染或潜伏感染的细胞后，观察并定量了5′-LTR中CpG岛甲基化对HIV-1表达的有效抑制。ZF 2-DNMT 1对潜伏感染细胞中HIV的有效抑制是稳定的，并且可以持续约40代细胞。ZF 2-DNMT 1仅在细胞增殖期间观察到细胞毒性。总之，我们的研究结果证明了这种新方法用于抗HIV-1治疗的潜力。
HIV-1 inserts its proviral DNA into the infected host cells, by which HIV proviral DNA can then be duplicated along with each cell division. Thus, provirus cannot be eradicated completely by current antiretroviral therapy. We have developed an innovative strategy to silence the HIV provirus by targeted DNA methylation on the HIV promoter region. We genetically engineered a chimeric DNA methyltransferase 1 composed of designed zinc-finger proteins to become ZF2 DNMT1. After transient transfection of the molecular clone encoding this chimeric protein into HIV-1 infected or latently infected cells, efficient suppression of HIV-1 expression by the methylation of CpG islands in 5′-LTR was observed and quantified. The effective suppression of HIV in latently infected cells by ZF2-DNMT1 is stable and can last through about 40 cell passages. Cytotoxic caused by ZF2-DNMT1 was only observed during cellular proliferation. Taken together, our results demonstrate the potential of this novel approach for anti-HIV-1 therapy.
DOI：
10.3390/v5020753
发表时间：
2013-02-21
期刊：
Viruses
影响因子：
--
作者：
Fior J
通讯作者：
Fior J