RNA interference directed to CDK2 inhibits HIV-1 transcription
RNA interference directed to CDK2 inhibits HIV-1 transcription
复制标题
DOI：
10.1016/j.virol.2005.06.041
复制
发表时间：
2005-10-25
期刊：
影响因子：
3.7
通讯作者：
Nekhai, S
中科院分区：
文献类型：
--
作者：
Ammosova, T;Berro, R;Nekhai, S
我们以前报道，细胞周期依赖性激酶2（CDK 2）是所需的人类免疫缺陷病毒-1（HIV-1）的Tat依赖性转录在体外。在本研究中，在培养的HEK 293 T细胞中，CDK 2特异性RNA干扰抑制CDK 2表达和Tat诱导的HIV-1非整合启动子转录，但不抑制基础HIV-1转录或CMV或β-肌动蛋白启动子转录。此外，CDK 2特异性RNA干扰抑制Tat诱导的HeLa-CD 4-LTR-β-gal细胞中整合的HIV-1启动子的转录，并有效阻断OM 10.1细胞中TNF α诱导的HIV-1病毒复制。CDK 2特异性RNA干扰对细胞周期进程没有影响，但它增强了TNF α诱导的OM 10.1细胞凋亡。我们的研究结果表明，CDK 2参与Tat介导的HIV-1转录，并可能作为一个潜在的治疗靶点。(c)2005年爱思唯尔公司All rights reserved.
We previously reported that cell cycle-dependent kinase 2 (CDK2) is required for human immunodeficiency virus-1 (HIV-1) Tat-dependent transcription in vitro. In the present study, CDK2-specific RNA interference in cultured HEK293T cells inhibited CDK2 expression and Tat-induced HIV-1 transcription from non-integrated HIV-1 promoter but not basal HIV-1 transcription or transcription from CMV or beta-actin promoters. Also, CDK2-specific RNA interference inhibited Tat-induced transcription from the integrated HIV-1 promoter in HeLa-CD4-LTR-beta-gal cells and potently blocked TNF alpha-induced HIV-1 viral replication in OM 10.1 cells. CDK2-specific RNA interference did not have an effect on cell cycle progression, but it augmented TNF alpha-induced apoptosis of OM 10.1 cells. Our results indicate that CDK2 participates in Tat-mediated HIV-1 transcription and may serve as a potential therapeutic target. (c) 2005 Elsevier Inc. All rights reserved.