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首页> 外文期刊>BMC Biotechnology >A suicide gene approach using the human pro-apoptotic protein tBid inhibits HIV-1 replication
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A suicide gene approach using the human pro-apoptotic protein tBid inhibits HIV-1 replication

机译：使用人类促凋亡蛋白tBid的自杀基因方法抑制HIV-1复制

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Background Regulated expression of suicide genes is a powerful tool to eliminate specific subsets of cells and will find widespread usage in both basic and applied science. A promising example is the specific elimination of human immunodeficiency virus type 1 ( HIV-1 ) infected cells by LTR-driven suicide genes. The success of this approach, however, depends on a fast and effective suicide gene, which is expressed exclusively in HIV-1 infected cells. These preconditions have not yet been completely fulfilled and, thus, success of suicide approaches has been limited so far. We tested truncated Bid (tBid), a human pro-apoptotic protein that induces apoptosis very rapidly and efficiently, as suicide gene for gene therapy against HIV-1 infection. Results When tBid was introduced into the HIV-1 LTR-based, Tat- and Rev-dependent transgene expression vector pLRed(INS)2R, very efficient induction of apoptosis was observed within 24 hours, but only in the presence of both HIV-1 regulatory proteins Tat and Rev. Induction of apoptosis was not observed in their absence. Cells containing this vector rapidly died when transfected with plasmids containing full-length viral genomic DNA, completely eliminating the chance for HIV-1 replication. Viral replication was also strongly reduced when cells were infected with HIV-1 particles. Conclusions This suicide vector has the potential to establish a safe and effective gene therapy approach to exclusively eliminate HIV-1 infected cells before infectious virus particles are released.
机译：背景技术自杀基因的调控表达是消除特定细胞亚群的有力工具，将在基础科学和应用科学中得到广泛应用。一个有希望的例子是通过LTR驱动的自杀基因特异性消除人类1型免疫缺陷病毒（HIV-1）感染的细胞。但是，这种方法的成功取决于快速有效的自杀基因，该基因仅在感染HIV-1的细胞中表达。这些前提条件尚未完全实现，因此，迄今为止，自杀方法的成功受到限制。我们测试了截短的Bid（tBid），这是一种人类促凋亡蛋白，可以快速有效地诱导细胞凋亡，作为自杀基因用于HIV-1感染的基因治疗。结果将tBid引入基于HIV-1 LTR的，依赖于Tat和Rev的转基因表达载体pLRed（INS） 2 R时，非常有效地诱导了在24小时内观察到凋亡，但仅在同时存在HIV-1调节蛋白Tat和Rev的情况下观察到。用含有全长病毒基因组DNA的质粒转染含有该载体的细胞后，它们会迅速死亡，从而完全消除了HIV-1复制的机会。当细胞感染HIV-1颗粒时，病毒的复制也大大减少。结论该自杀载体具有建立安全有效的基因治疗方法的潜力，可以在感染性病毒颗粒释放之前专门清除HIV-1感染的细胞。

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