The HIV-1 DNA flap stimulates HIV vector-mediated cell transduction in the brain
The HIV-1 DNA flap stimulates HIV vector-mediated cell transduction in the brain
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DOI：
10.1038/88115
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发表时间：
2001-05-01
影响因子：
46.9
通讯作者：
Charneau, P
中科院分区：
文献类型：
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作者：
Zennou, V;Serguera, C;Charneau, P
在HIV-1逆转录过程中，正链DNA在中央多嘌呤段（cPPT）的中央起始和在中央终止序列（CTS）的中央终止导致形成三链DNA结构：HIV-1中央DNA瓣。我们最近报道了DNA瓣作为HIV-1基因组核输入的顺式活性决定因子。常用的HIV-1衍生载体（HR载体）缺乏中央DNA瓣。在这里，我们报告说，这种DNA皮瓣序列插入HR载体（TRIP载体）提高基因转导神经细胞，离体和体内，在大鼠大脑。当神经细胞暴露于增加浓度的TRIP载体颗粒时，转基因表达与载体的剂量相关。该效应与使用HR向量时观察到的平台期形成对比。我们进一步证明，TRIP载体获得的体内转导效率的增加是由于其基因组核输入的刺激。
During HIV-1 reverse transcription, central initiation of the plus-strand DNA at the central polypurine tract (cPPT) and central termination at the central termination sequence (CTS) lead to the formation of a three-stranded DNA structure: the HIV-1 central DNA flap. We recently reported that the DNA flap acts as a cis-active determinant of HIV-1 genome nuclear import. Commonly employed HIV-1-derived vectors (HR vectors) lack the central DNA flap. Here we report that the insertion of this DNA flap sequence into HR vectors (TRIP vectors) improves gene transduction in neural cells, ex vivo and in vivo, in rat brain. When neural cells are exposed to increasing concentrations of TRIP vector particles, transgene expression correlates with the dose of vector. This effect contrasts with the plateau observed when using an HR vector. We further demonstrate that the increase of in vivo transduction efficiency obtained with TRIP vectors is due to the stimulation of their genome nuclear import.