An inducible human immunodeficiency virus type 1 (HIV-1) vector which effectively suppresses HIV-1 replication

An inducible human immunodeficiency virus type 1 (HIV-1) vector which effectively suppresses HIV-1 replication
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DOI:
10.1128/jvi.73.9.7671-7677.1999
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发表时间:
1999-09-01
影响因子:
5.4
通讯作者:
Chen, ISY
Chen, ISY
中科院分区:
医学2区
文献类型:
--
作者:
An, DS;Morizono, K;Chen, ISY

文献摘要

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最近,已经开发了基于人类免疫缺陷病毒1型(HIV-1)基因组的基因治疗载体。在这里,我们创建了一个HIV-1载体,它对所有HIV-1基因都有缺陷,但它保留了有效包装,感染和表达所需的顺式作用元件。在由该载体转导的T细胞中,载体表达较低,但在HIV-1感染后被有效诱导。值得注意的是,尽管HIV-1载体不含特异性抗HIV-1治疗基因,但仅载体的存在就足以抑制HIV-1感染的传播。抑制机制可能是在竞争有效包装或逆转录所需的限制性底物的水平上,从而选择抑制野生型HIV-1的繁殖。这些结果为新型HIV-1载体在HIV-1疾病中的潜在应用提供了概念证据。
Recently, gene therapy vectors based upon the human immunodeficiency virus type 1 (HIV-1) genome have been developed. Here, we create an HIV-1 vector which is defective for all HIV-1 genes, but which maintains cis-acting elements required for efficient packaging, infection, and expression. In T cells transduced by this vector, vector expression is low but efficiently induced following HIV-1 infection. Remarkably, although the HIV-1 vector does not contain specific anti-HIV-1 therapeutic genes, the presence of the vector alone is sufficient to inhibit the spread of HIV-1 infection. The mechanism of inhibition is likely to be at the level of competition for limiting substrates required for either efficient packaging or reverse transcription, thereby selecting against propagation of wild-type HIV-1. These results provide proof of a concept for potential application of a novel HIV-1 vector in HIV-1 disease.