Hiebenthal-Millow Kirsten, Pöhlmann Stefan, Münch Jan, Kirchhoff Frank
Institute for Clinical and Molecular Virology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
Virology. 2004 Jul 1;324(2):501-9. doi: 10.1016/j.virol.2004.04.007.
Promoter activity of the HIV-1 long terminal repeat (LTR) is largely dependent on intact NF-kB and SpI binding sites in the U3 region. In contrast, upstream LTR sequences allow efficient simian immunodeficiency virus (SIVmac) transcription in the absence of the core enhancer promoter region. In the present study, we investigated whether the regulation of HIV-2 Rod LTR activity is more reminiscent of HIV-1 having the same host or of SIVmac239 belonging to the same phylogenetic group. Viral promoter activity was studied in the context of the integrated provirus using both single cycle assays with pseudotyped luciferase reporter viruses and replication-competent HIV-2 LTR mutants. Our results demonstrate that intact SpI binding sites are important for both HIV-2 and SIVmac LTR activity in T cells and monocyte-derived macrophages. In contrast, deletion of the NF-kB binding site or of upstream regulatory sequences impaired HIV-2 Rod LTR activity but had little effect on SIVmac239 promoter function. Thus, similar to HIV-1, regulation of HIV-2 LTR promoter activity shows a low degree of functional redundancy possibly suggesting a specific adaptation to the human host.
HIV-1长末端重复序列（LTR）的启动子活性很大程度上依赖于U3区域完整的NF-κB和SpI结合位点。相比之下，上游LTR序列在没有核心增强子启动子区域的情况下能实现高效的猿猴免疫缺陷病毒（SIVmac）转录。在本研究中，我们调查了HIV-2罗德株LTR活性的调控更类似于具有相同宿主的HIV-1，还是更类似于属于同一进化组的SIVmac239。我们使用假型荧光素酶报告病毒的单周期测定法和具有复制能力的HIV-2 LTR突变体，在整合前病毒的背景下研究了病毒启动子活性。我们的结果表明，完整的SpI结合位点对T细胞和单核细胞衍生巨噬细胞中的HIV-2和SIVmac LTR活性都很重要。相比之下，NF-κB结合位点或上游调控序列的缺失会损害HIV-2罗德株LTR活性，但对SIVmac239启动子功能影响很小。因此，与HIV-1类似，HIV-2 LTR启动子活性的调控显示出较低程度的功能冗余，这可能表明其对人类宿主有特定适应性。
