Long terminal repeat promoter/enhancer activity of different subtypes of HIV type 1
Long terminal repeat promoter/enhancer activity of different subtypes of HIV type 1
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DOI：
10.1089/088922299310197
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发表时间：
1999-09-20
影响因子：
1.5
通讯作者：
Vahlne, A
中科院分区：
文献类型：
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作者：
Naghavi, MH;Schwartz, S;Vahlne, A
HIV-1前病毒基因组的转录受病毒调节蛋白和与HIV-1的病毒长末端重复（LTR）区域相互作用的细胞转录因子之间的复杂相互作用调节。然而，已经鉴定了几种可以与HIV-1 LTR相互作用的细胞转录因子;所有这些因子的意义尚不清楚。在这项研究中，我们的特点是不同亚型的HIV-1的LTR区域的核苷酸序列和启动子活性。对来自10个不同地理区域的29个感染个体的外周血单核细胞的HIV-1的LTR区域进行测序，并进一步分析在瞬时转染HeLa细胞中，在报告基因的背景下和在完整病毒基因组的背景下的启动子/增强子活性。我们发现了多种HIV-1毒株的几种亚型特异性LTR序列，例如在C亚型毒株的LTR中产生潜在的第三个NF-κ B位点的插入。NRE中的USF结合位点也包含亚型特异性序列。有趣的是，亚型C LTR的启动子/增强子活性高于本文分析的其他亚型（亚型A、B、D、E和G）的活性，表明潜在的第三NF-κ B位点可能赋予更高的LTR活性，或者亚型C NRE可能效力较低。因此，我们的数据表明，LTR的遗传多样性可能导致HIV-1亚型具有不同的复制特性。
Transcription of the HIV-1 provirus genome is regulated by a complex interplay between viral regulatory proteins and cellular transcription factors that interact with the viral long terminal repeat (LTR) region of HIV-1, However, several cellular transcription factors have been identified that can interact with the HIV-1 LTR; the significance of all of these factors is not clearly understood. In this study we have characterized the LTR region of different subtypes of HIV-1 with regard to nucleotide sequence and promoter activity. The LTR regions of HIV-1 from peripheral blood mononuclear cells of 29 infected individuals originating from 10 different geographical regions were sequenced and further analyzed for promoter/enhancer activity in transient transfection of HeLa cells, in the context of a reporter gene and in the context of the complete virus genome. We found several subtype-specific LTR sequences of the various HIV-1 strains, such as an insertion that created a potential third NF-kappa B site in the LTR of the subtype C strains. The USF-binding site in the NRE also contained subtype-specific sequences. Interestingly, the promoter/enhancer activities of the subtype C LTRs were higher than the activities of the other subtypes analyzed here (subtypes A, B, D, E, and G), suggesting that the potential third NF-kappa B site may confer higher LTR activity or that the subtype C NRE may be less potent. Thus, our data suggest that genetic diversity of the LTR may result in HIV-1 subtypes with different replicative properties.