Pomerantz R J, Feinberg M B, Trono D, Baltimore D
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
J Exp Med. 1990 Jul 1;172(1):253-61. doi: 10.1084/jem.172.1.253.
Lipopolysaccharide (LPS) potently stimulates human immunodeficiency virus type 1-long terminal repeat (HIV-1-LTR) CAT constructs transfected into monocyte/macrophage-like cell lines but not a T cell line. This effect appears to be mediated through the induction of nuclear factor kappa B (NF-kappa B). Electrophoretic mobility shift assays demonstrate that LPS induces a DNA binding activity indistinguishable from NF-kappa B in U937 and THP-1 cells. LPS is also shown to dramatically increase HIV-1 production from a chronically infected monocyte/macrophage-like cloned cell line, U1, which produces very low levels of HIV-1 at baseline. The stimulation of viral production from this cell line occurs only if these cells are treated with granulocyte/macrophage colony-stimulating factor (GM-CSF) before treatment with LPS. This stimulation of HIV-1 production is correlated with an increase in the level of HIV-1 RNA and and activation of NF-kappa B. LPS is not able to induce HIV-1 production in a cloned T cell line. The effect of LPS on HIV-1 replication occurs at picogram per milliliter concentrations and may be clinically significant in understanding the variability of the natural history of HIV-1 infection.
脂多糖(LPS)能有效刺激转染至单核细胞/巨噬细胞样细胞系而非T细胞系中的人免疫缺陷病毒1型长末端重复序列(HIV-1-LTR)CAT构建体。这种效应似乎是通过诱导核因子κB(NF-κB)介导的。电泳迁移率变动分析表明,LPS在U937和THP-1细胞中诱导出一种与NF-κB难以区分的DNA结合活性。LPS还被证明可显著增加来自慢性感染的单核细胞/巨噬细胞样克隆细胞系U1的HIV-1产生,该细胞系在基线时产生的HIV-1水平非常低。只有在用LPS处理之前先用粒细胞/巨噬细胞集落刺激因子(GM-CSF)处理这些细胞,才能刺激该细胞系产生病毒。这种对HIV-1产生的刺激与HIV-1 RNA水平的增加以及NF-κB的激活相关。LPS无法在克隆的T细胞系中诱导HIV-1产生。LPS对HIV-1复制的影响在每毫升皮克浓度下就会出现,在理解HIV-1感染自然史的变异性方面可能具有临床意义。