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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.

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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