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来自合胞体诱导型和非合胞体诱导型1型人类免疫缺陷病毒的长末端重复序列的遗传变异性和功能

Genetic variability and function of the long terminal repeat from syncytium-inducing and non-syncytium-inducing human immunodeficiency virus type 1.

作者信息

Simm M, Chao W, Pekarskaya O, Sova P, Gupta P, Balachandran R, Volsky D J

机构信息

Molecular Virology Laboratory, St. Luke's-Roosevelt Hospital Center, Columbia University, New York, New York 10019, USA.

出版信息

AIDS Res Hum Retroviruses. 1996 Jun 10;12(9):801-9. doi: 10.1089/aid.1996.12.801.

DOI:10.1089/aid.1996.12.801
PMID:8738432
Abstract

We analyzed sequence variability and function of the long terminal repeat (LTR) from syncytium-inducing (SI) and non-syncytium-inducing (NSI) HIV-1. Twenty LTR DNA clones were obtained by polymerase chain reaction amplification and molecular cloning from short-term cultures of SI and NSI viruses from an AIDS patient and two asymptomatic individuals, respectively. All the LTR clones tested contained multiple nucleotide changes (mostly G-to-A transitions), compared to the subtype B consensus sequence, which were clustered within the negative regulatory element, including NF-AT, USF, and TCF-1 alpha binding sites. The core promoter/TAR region sequences were highly conserved. The basal and Tat-mediated transcriptional activities of selected LTR clones tested were 0.1 to 1 and 0.2 to 0.5 times that of the control, respectively, regardless of the SI or NSI origin of the clones. Phylogenetic analysis revealed interi-solate sequence divergence in the LTR that was similar but not identical to previously analyzed vif sequences from the same samples. In particular, the inter-isolate distances from reference sequences differed for the LTR and vif. This raises the possibility that recombination occurred between corresponding LTR and vif loci of the quasi-species present in the isolates described here.

摘要

我们分析了来自合胞体诱导型(SI)和非合胞体诱导型(NSI)HIV-1的长末端重复序列(LTR)的序列变异性和功能。分别从一名艾滋病患者以及两名无症状个体的SI和NSI病毒短期培养物中,通过聚合酶链反应扩增和分子克隆获得了20个LTR DNA克隆。与B亚型共有序列相比,所有测试的LTR克隆都包含多个核苷酸变化(主要是G到A的转换),这些变化聚集在负调控元件内,包括NF-AT、USF和TCF-1α结合位点。核心启动子/TAR区域序列高度保守。无论克隆的来源是SI还是NSI,所测试的选定LTR克隆的基础转录活性和Tat介导的转录活性分别是对照的0.1至1倍和0.2至0.5倍。系统发育分析揭示了LTR中分离株间的序列差异,这与先前分析的来自相同样本的vif序列相似但不完全相同。特别是,LTR和vif与参考序列的分离株间距离不同。这增加了在此描述的分离株中存在的准种的相应LTR和vif基因座之间发生重组的可能性。

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