Structural and functional properties of HIV-1-GER TAR sequences
Structural and functional properties of HIV-1-GER TAR sequences
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DOI：
10.1007/bf02253576
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发表时间：
1996-01-01
影响因子：
11
通讯作者：
Devaux, Christian
中科院分区：
文献类型：
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作者：
Emiliani, Stephane;Coudronniere, Nolwenn;Devaux, Christian
HIV-1-格尔长末端重复序列（LTR）的测序首次在HIV-1原代分离株中证实了TAR重复，称为TAR 1（核苷酸+1至+68）和TAR 2（核苷酸+69至+136）。这种TAR复制在CEM细胞中HIV-1-格尔分离株复制期间是稳定的。LTR-CAT报告基因构建体的分析表明，在达特反式激活下，HIV-1-格尔/LTR（含有TAR 1和TAR 2）的表达水平高于含有单个TAR序列的类似构建体（HIV-1-GER-DELTA-TAR）。在HIV 1-格尔/LTR中发现的两个转录起始位点中，只有最5'端的起始位点显示出功能活性。HIV-1-格尔5 '端mRNA的预测二级结构表明，它可能折叠成类似于HIV-2的双TAR发夹。最后，HIV-1-格尔达特蛋白显示与来自其它HIV-1分离株的达特蛋白的主要序列相似性，并且显然与HIV-2达特蛋白无关。这项工作提供了HIV-1中TAR序列重复的第一个证据，它增加了达特的反式激活效率。
Sequencing of HIV-1-GER long terminal repeat (LTR) has demonstrated, for the first time in an HIV-1 primary isolate, a TAR duplication referred to as TAR1 (nucleotides +1 through +68) and TAR2 (nucleotides +69 through +136). This TAR duplication is stable during replication of HIV-1-GER isolate in CEM cells. Analysis of LTR-CAT reporter constructs demonstrated that under Tat transactivation the HIV-1-GER/LTR (containing TAR1 and TAR2) was expressed at a higher level than a similar construct (HIV-1-GER-DELTA-TAR) containing a single TAR sequence. Among the two transcription initiation sites found in the HIV1-GER/LTR, only the most 5' start site was shown to be functionally active. The predicted secondary structure of the 5'-end mRNAs of HIV-1-GER suggests it may fold into a double TAR hairpin which resembles that of HIV-2. Finally, HIV-1-GER Tat protein shows primary sequence similarity with Tat proteins from other isolates of HIV-1 and is apparently unrelated to HIV-2 Tat proteins. This work provides the first evidence of a TAR sequence duplication in HIV-1 which increases the efficiency of transactivation by Tat.