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巨细胞病毒和人类免疫缺陷病毒2型(HIV-2)反式激活基因对HIV-2基因表达的刺激作用

Stimulation of the human immunodeficiency virus type 2 (HIV-2) gene expression by the cytomegalovirus and HIV-2 transactivator gene.

作者信息

Arya S K, Sethi A

机构信息

Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.

出版信息

AIDS Res Hum Retroviruses. 1990 May;6(5):649-58. doi: 10.1089/aid.1990.6.649.

DOI:10.1089/aid.1990.6.649
PMID:1972889
Abstract

Human immunodeficiency virus (HIV) often causes latent infection. Transactivation by some DNA viruses has been implicated in inducing HIV-1 replication and pathogenesis. The transactivator (IE-2) gene of the human cytomegalovirus (CMV) can enhance HIV-2 as well as HIV-1 gene expression in vitro. This inducer can act in concert with the HIV-2 tat gene and T-cell activation in enhancing gene expression in human CD4+ lymphocytes. While the HIV-2 and HIV-1 tat genes and T-cell activators apparently employ independent modes of action, the CMV transactivator in combination with the HIV-2 tat or T-cell activators may employ a gene activation pathway with some common and some distinct components. Both HIV-2 and CMV transactivators enhance HIV-2 gene expression by transcriptional activation involving transcript initiation as well as elongation, with CMV transactivator affecting elongation more than the initiation. A significant proportion of transcripts appear to terminate prematurely in the absence of transactivators. Deletion mutation analysis of the HIV-2 long terminal repeat (LTR) suggests that the element that responds to CMV transactivation in human CD4+ lymphocytes is either a diffuse one or located downstream of the HIV-2 enhancer element.

摘要

人类免疫缺陷病毒(HIV)常引发潜伏感染。一些DNA病毒的反式激活作用被认为与诱导HIV-1复制及发病机制有关。人巨细胞病毒(CMV)的反式激活因子(IE-2)基因在体外可增强HIV-2以及HIV-1的基因表达。该诱导剂能与HIV-2 tat基因协同作用,并在激活人CD4+淋巴细胞基因表达过程中发挥作用。虽然HIV-2和HIV-1 tat基因以及T细胞激活剂显然采用独立的作用模式,但CMV反式激活因子与HIV-2 tat或T细胞激活剂联合使用时,可能采用一种具有一些共同和一些不同成分的基因激活途径。HIV-2和CMV反式激活因子均通过涉及转录起始及延伸的转录激活来增强HIV-2基因表达,其中CMV反式激活因子对延伸的影响大于起始。在没有反式激活因子的情况下,相当一部分转录本似乎会过早终止。对HIV-2长末端重复序列(LTR)的缺失突变分析表明,在人CD4+淋巴细胞中对CMV反式激活作出反应的元件要么是一个弥散元件,要么位于HIV-2增强子元件的下游。

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引用本文的文献

1
The effects of cytomegalovirus on human immunodeficiency virus replication in brain-derived cells correlate with permissiveness of the cells for each virus.巨细胞病毒对脑源细胞中人类免疫缺陷病毒复制的影响与细胞对每种病毒的易感性相关。
J Virol. 1994 Feb;68(2):959-73. doi: 10.1128/JVI.68.2.959-973.1994.
2
A discrete cis element in the human immunodeficiency virus long terminal repeat mediates synergistic trans activation by cytomegalovirus immediate-early proteins.人类免疫缺陷病毒长末端重复序列中的一个离散顺式元件介导巨细胞病毒立即早期蛋白的协同反式激活作用。
J Virol. 1991 Dec;65(12):6735-42. doi: 10.1128/JVI.65.12.6735-6742.1991.
3
Modulation of T-cell activation through protein kinase C- or A-dependent signalling pathways synergistically increases human immunodeficiency virus long terminal repeat induction by cytomegalovirus immediate-early proteins.
通过蛋白激酶C或A依赖性信号通路调节T细胞活化可协同增强巨细胞病毒立即早期蛋白对人免疫缺陷病毒长末端重复序列的诱导作用。
J Virol. 1991 Oct;65(10):5477-84. doi: 10.1128/JVI.65.10.5477-5484.1991.