Laughlin M A, Chang G Y, Oakes J W, Gonzalez-Scarano F, Pomerantz R J
Dorrance H. Hamilton Laboratories, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Aug 1;9(4):332-9.
Nuclear factor-kappa B (NF-kappa B) has been shown to play a central role in stimulating human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR)-directed viral gene expression. We have previously described a cell line (TE671/RD) that fails to respond to phorbol myristate acetate (PMA) or tumor necrosis factor-alpha (TNF-alpha) in terms of amplifying HIV-1 LTR-driven gene expression unless it is concurrently treated with sodium butyrate. It was not determined whether this lack of response stemmed from an inability of these cells to produce free NF-kappa B or from ineffectual interaction of this sequence-specific transcriptional factor with its target. We now show that these cells are in fact capable of inducing a free nuclear NF-kappa B-binding activity when stimulated with PMA but not when treated with sodium butyrate alone. Furthermore, we show that sodium butyrate alone is equally potent in stimulating HIV-1 LTR-directed gene expression in latently infected U1 and ACH-2 cells in the absence of induction of nuclear NF-kappa B, as compared with PMA, which induces NF-kappa B activation in these cells. We also show that stimulation of HIV-1 expression in U1 cells with sodium butyrate is not blocked by N-acetylcysteine, whereas that of PMA stimulation is blocked. These observations are discussed in the context of a model where chromatin structure participates in the maintenance of restricted HIV-1 viral gene expression in these cells.
核因子-κB（NF-κB）已被证明在刺激人类免疫缺陷病毒1型（HIV-1）长末端重复序列（LTR）驱动的病毒基因表达中起核心作用。我们之前描述过一种细胞系（TE671/RD），该细胞系在放大HIV-1 LTR驱动的基因表达方面，对佛波酯肉豆蔻酸酯（PMA）或肿瘤坏死因子-α（TNF-α）无反应，除非同时用丁酸钠处理。尚未确定这种无反应是源于这些细胞无法产生游离的NF-κB，还是源于这种序列特异性转录因子与其靶标的无效相互作用。我们现在表明，这些细胞在用PMA刺激时实际上能够诱导游离的核NF-κB结合活性，但单独用丁酸钠处理时则不能。此外，我们表明，与在这些细胞中诱导NF-κB激活的PMA相比，在没有诱导核NF-κB的情况下，单独的丁酸钠在刺激潜伏感染的U1和ACH-2细胞中HIV-1 LTR驱动的基因表达方面同样有效。我们还表明，丁酸钠对U1细胞中HIV-1表达的刺激不会被N-乙酰半胱氨酸阻断，而PMA刺激则会被阻断。在染色质结构参与维持这些细胞中受限的HIV-1病毒基因表达的模型背景下讨论了这些观察结果。
