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DNA病毒对人类免疫缺陷病毒长末端重复序列的反式激活作用

Trans-activation of the human immunodeficiency virus long terminal repeat sequence by DNA viruses.

作者信息

Gendelman H E, Phelps W, Feigenbaum L, Ostrove J M, Adachi A, Howley P M, Khoury G, Ginsberg H S, Martin M A

出版信息

Proc Natl Acad Sci U S A. 1986 Dec;83(24):9759-63. doi: 10.1073/pnas.83.24.9759.

Abstract

To investigate whether DNA viruses can augment gene expression of the human immunodeficiency virus (HIV), cotransfection experiments were carried out in which a recombinant plasmid containing the HIV long terminal repeat (LTR) linked to the chloramphenicol acetyltransferase (CAT) gene was transfected into cultured cells along with plasmids containing DNA from various distinct classes of DNA viruses. Molecular clones containing JC virus, BK virus, lymphotropic papovavirus, bovine papilloma virus, type 1 herpes simplex virus (HSV-1), and varicella-zoster virus sequences increased CAT expression directed by the HIV LTR. Trans-activation of the HIV LTR varied in different cell lines, but in each case the HIV tat gene product elicited the greatest stimulation. Primer-extension assays specific for HIV LTR mRNA revealed increased levels of steady-state RNA following transfection with HIV tat as well as with several of the DNA viruses. Virus-specific RNA expression paralleled the stimulation of CAT activity. More-than-additive effects were observed at both the RNA and protein levels when tat plus type 1 herpes simplex virus DNAs or tat plus JC virus DNAs were transfected into cells with the HIV LTR-CAT plasmid. These data suggest that coinfection of cells by HIV and some DNA viruses can stimulate the expression of HIV.

摘要

为了研究DNA病毒是否能够增强人类免疫缺陷病毒(HIV)的基因表达,进行了共转染实验,即将含有与氯霉素乙酰转移酶(CAT)基因相连的HIV长末端重复序列(LTR)的重组质粒,与含有来自不同种类DNA病毒的DNA的质粒一起转染到培养细胞中。含有JC病毒、BK病毒、嗜淋巴细胞乳头瘤病毒、牛乳头瘤病毒、1型单纯疱疹病毒(HSV-1)和水痘带状疱疹病毒序列的分子克隆增加了HIV LTR指导的CAT表达。HIV LTR的反式激活在不同细胞系中有所不同,但在每种情况下,HIV tat基因产物都引发了最大的刺激作用。针对HIV LTR mRNA的引物延伸分析显示,在用HIV tat以及几种DNA病毒转染后,稳态RNA水平升高。病毒特异性RNA表达与CAT活性的刺激作用平行。当将tat加1型单纯疱疹病毒DNA或tat加JC病毒DNA与HIV LTR-CAT质粒一起转染到细胞中时,在RNA和蛋白质水平均观察到了超相加效应。这些数据表明,HIV与某些DNA病毒的细胞共感染能够刺激HIV的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e4c/387220/c3153bbf1efe/pnas00328-0495-a.jpg

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