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慢性感染的人T细胞克隆中人类免疫缺陷病毒1型表达的单核因子调控

Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T cell clone.

作者信息

Clouse K A, Powell D, Washington I, Poli G, Strebel K, Farrar W, Barstad P, Kovacs J, Fauci A S, Folks T M

机构信息

Georgetown University, Department of Microbiology, Washington, D.C. 20007.

出版信息

J Immunol. 1989 Jan 15;142(2):431-8.

PMID:2463307
Abstract

A T cell clone (ACH-2) derived from T cells infected with HIV-1 was found to produce HIV-1 in response to stimulation with a monokine-enriched supernatant prepared by culturing human monocyte/macrophages with bacterial LPS (LPS-MO SN). Monokine induction of ACH-2 cells resulted in augmented virus production reflected by an increase in reverse transcriptase activity and in the synthesis of all major viral proteins. Examination of the cells by indirect immunofluorescence revealed that 10 to 15% of uninduced cells constitutively expressed HIV proteins, whereas 100% showed positive immunofluorescence in response to LPS-MO SN. This induction of virus by LPS-MO SN resulted in approximately a 100-fold increase of infectious virus production over uninduced ACH-2 cells. LPS alone could not induce HIV-1 expression, whereas LPS-MO SN resulted in the greatest virus expression. Cell separation studies confirmed the source of the inducing factor(s) to be cells bearing the mature monocyte/macrophage marker, Leu M3. Biochemical fractionation of the LPS-MO SN suggested that one or more factors, having apparent Mr of approximately 45 kDa, were involved in this induction. Absorption of the LPS-MO SN with immunoaffinity gels specific for human TNF-alpha was shown to completely remove the HIV inducing activity for the ACH-2 cell line.

摘要

从感染了HIV-1的T细胞中获得的一个T细胞克隆(ACH-2),被发现可在受到一种富含单核因子的上清液刺激时产生HIV-1,该上清液是通过用细菌脂多糖(LPS-MO SN)培养人单核细胞/巨噬细胞制备的。单核因子对ACH-2细胞的诱导导致病毒产生增加,这通过逆转录酶活性的增加以及所有主要病毒蛋白的合成增加得以体现。通过间接免疫荧光对细胞进行检测发现,10%至15%的未诱导细胞组成性表达HIV蛋白,而在受到LPS-MO SN刺激后,100%的细胞呈现阳性免疫荧光。LPS-MO SN对病毒的这种诱导导致感染性病毒产量比未诱导的ACH-2细胞增加了约100倍。单独的LPS不能诱导HIV-1表达,而LPS-MO SN导致最大程度的病毒表达。细胞分离研究证实诱导因子的来源是带有成熟单核细胞/巨噬细胞标志物Leu M3的细胞。对LPS-MO SN进行生化分级分离表明,一种或多种表观分子量约为45 kDa的因子参与了这种诱导。用针对人TNF-α的免疫亲和凝胶吸收LPS-MO SN,结果显示可完全消除其对ACH-2细胞系的HIV诱导活性。

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