Silencing of human immunodeficiency virus long terminal repeat expression by an adenovirus E1a mutant.
Silencing of human immunodeficiency virus long terminal repeat expression by an adenovirus E1a mutant.
复制标题
腺病毒 E1a 突变体沉默人类免疫缺陷病毒长末端重复表达。
DOI：
10.1073/pnas.87.4.1310
复制
发表时间：
1990
影响因子：
11.1
通讯作者：
Chinnadurai,G
中科院分区：
文献类型：
--
作者：
Ventura,AM;Arens,MQ;Srinivasan,A;Chinnadurai,G
人类免疫缺陷病毒（HIV）长末端重复序列（LTR）的基因表达受到病毒tat基因的强烈刺激。HIV LTR也被几种物理和化学试剂和异源病毒基因（包括腺病毒E1a）激活。由于E1a具有可分离的转录激活和抑制功能，我们利用一个反显性E1a突变体研究了E1a对HIV LTR表达的负调控作用。突变体hr5强烈抑制LTR的基础活性以及异源药物如巨细胞病毒即时早期基因或dna损伤剂如丝裂霉素C和紫外线照射对LTR的反式激活。此外，hr5也显著抑制了该基因介导的反式激活。hr5对HIV LTR表达的抑制似乎至少部分是由HIV增强子的抑制介导的，因为由含有HIV-1增强子替代的人t细胞白血病病毒I LTR组成的增强子测试系统的活性被hr5严重抑制。HIV-1前病毒DNA与hr5 DNA共转染可显著减少HIV的产生。
Gene expression from the human immunodeficiency virus (HIV) long terminal repeat (LTR) is strongly stimulated by the viral tat gene. The HIV LTR is also activated by several physical and chemical agents and heterologous viral genes, including adenovirus E1a. As E1a has separable transcriptional activation and repression functions, we examined the negative regulatory effects of E1a on the expression of the HIV LTR by using a trans-dominant E1a mutant. Mutant hr5 strongly suppressed the basal activity of the LTR as well as trans-activation of the LTR by heterologous agents such as the cytomegalovirus immediate early gene or DNA-damaging agents such as mitomycin C and UV irradiation. In addition, hr5 also caused significant suppression of tat gene-mediated trans-activation. The suppression of HIV LTR expression by hr5 appears to be mediated, at least in part, by the repression of the HIV enhancer, as the activity of an enhancer test system composed of the human T-cell leukemia virus I LTR containing an HIV-1 enhancer substitution was severely repressed by hr5. Cotransfection of HIV-1 proviral DNA with hr5 DNA resulted in a significant reduction of HIV production.