Department of Life and Environmental Sciences, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan.
FEBS Lett. 2011 Nov 4;585(21):3367-71. doi: 10.1016/j.febslet.2011.09.029. Epub 2011 Sep 29.
The human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) contains binding sites for several host transcription factors that contribute to HIV-1 gene expression. Although previous reports have indicated that HIV-1 Nef positively or negatively regulates HIV-1 gene expression, the precise molecular mechanisms by which this occurs remain largely unknown. In this study, we report that Nef suppressed LTR-driven transcription only in the presence of HIV-1 Tat, which was localized to the cytoplasm and degraded by the proteasome. However, the depletion of Hsp70 was found to reduce the suppressive effect of Nef on HIV-1 gene expression. These results suggest that Nef suppresses Hsp70-mediated HIV-1 Tat activation.
人类免疫缺陷病毒 1 型（HIV-1）长末端重复序列（LTR）包含多个宿主转录因子的结合位点，这些因子有助于 HIV-1 基因表达。尽管先前的报告表明 HIV-1 Nef 正向或负向调节 HIV-1 基因表达，但这种作用的确切分子机制在很大程度上仍不清楚。在这项研究中，我们报告说，只有在 HIV-1 Tat 的存在下，Nef 才会抑制 LTR 驱动的转录，而 Tat 则位于细胞质中并被蛋白酶体降解。然而，发现耗尽 Hsp70 会降低 Nef 对 HIV-1 基因表达的抑制作用。这些结果表明，Nef 抑制 Hsp70 介导的 HIV-1 Tat 激活。
