Dysregulation through the NF-ΚB enhancer and TATA box of the human immunodeficiency virus type 1 subtype E promoter
Dysregulation through the NF-ΚB enhancer and TATA box of the human immunodeficiency virus type 1 subtype E promoter
复制标题
DOI：
10.1128/jvi.72.10.8446-8452.1998
复制
发表时间：
1998-10-01
影响因子：
5.4
通讯作者：
Essex, M
中科院分区：
文献类型：
--
作者：
Montano, MA;Nixon, CP;Essex, M
人类免疫缺陷病毒1型（HIV-1）基因型的全球多样性，称为亚型A至亚型J，是相当大的和不断增长的，然而，相对较少的研究提供了相关表型差异的证据。最近，我们证明了亚型扩展的长末端重复（LTR）区域内亚型特异性功能差异（M. A. Montano， V. A. Novitsky， J. T, Blackard， N. L. Cho， D， A. Katzenstein, and M, Essex， J, Virol, 71:8657-8665, 1997）。所有HIV-1E分离株均含有一个有缺陷的上游NF-kappa B位点和一个独特的TATA-TAR区。在这项研究中，我们证明了肿瘤坏死因子α (tnf - α)对HIV-1E LTR的刺激也受到损害，这与上游NF-kappa B位点缺陷一致。此外，对HIV-1E上游NF-kappa B位点的修复部分恢复了tnf - α的反应性。我们还表明，在凝胶移位试验中，相对于HIV-1B TATA寡核苷酸，跨越HIV-1E TATA盒的寡核苷酸在TBP-TFIIB-TATA复合物的组装效率降低。在转染试验中，当HIV-1E TATA被改变为标准的HIV-1B TATA序列（ATAAAA—>ATAATA）时，意外地降低了HIV-1E ltr驱动的报告基因的异源HIV-1B Tat和同源HIV-1E Tat的激活。然而，无论何种亚型，Tat激活都可以通过引入同源HIV-1B TAR来挽救。总的来说，这些观察结果表明，与HIV-1B相比，扩展的HIV-1E基因型可能进化出一种具有改变的NF-kappa B和TATA调控信号的替代启动子配置。
The global diversity of human immunodeficiency virus type 1 (HIV-1) genotypes, termed subtypes A to J, is considerable and growing, However, relatively few studies have provided evidence for an associated phenotypic divergence, Recently, we demonstrated subtype-specific functional differences within the long terminal repeat (LTR) region of expanding subtypes (M. A. Montano, V. A. Novitsky, J. T, Blackard, N. L. Cho, D, A. Katzenstein, and M, Essex, J, Virol, 71:8657-8665, 1997), Notably, all HIV-1E isolates were observed to contain a defective upstream NF-kappa B site and a unique TATA-TAR region. In this study, we demonstrate that tumor necrosis factor alpha (TNF-alpha) stimulation of the HIV-1E LTR was also impaired, consistent with a defective upstream NF-kappa B site. Furthermore, repair of the upstream NF-kappa B site within HIV-1E partially restored TNF-alpha responsiveness. We also show, in gel shift assays, that oligonucleotides spanning the HIV-1E TATA box displayed a reduced efficiency in the assembly of the TBP-TFIIB-TATA complex, relative to an HIV-1B TATA oligonucleotide. In transfection assays, the HIV-1E TATA, when changed to the canonical HIV-1B TATA sequence (ATAAAA-->ATAATA) unexpectedly reduces both heterologous HIV-1B Tat and cognate HIV-1E Tat activation of an HIV-1E LTR-driven reporter gene. However, Tat activation, irrespective of subtype, could be rescued by introducing a cognate HIV-1B TAR. Collectively, these observations suggest that the expanding HIV-1E genotype has likely evolved an alternative promoter configuration with altered NF-kappa B and TATA regulatory signals in contradistinction with HIV-1B.