Drastic decrease of transcription activity due to hypermutated long terminal repeat (LTR) region in different HIV-1 subtypes and recombinants.
Drastic decrease of transcription activity due to hypermutated long terminal repeat (LTR) region in different HIV-1 subtypes and recombinants.
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由于不同 HIV-1 亚型和重组体中长末端重复 (LTR) 区域的超突变，转录活性急剧下降。
DOI：
10.1016/j.antiviral.2010.08.007
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发表时间：
2010
影响因子：
7.6
通讯作者：
Á. Holguín
中科院分区：
文献类型：
--
作者：
Eva Ramírez de Arellano;J. Alcamí;Marisa López;V. Soriano;Á. Holguín
HIV-1基因表达的转录激活部分受作用于HIV-1长末端重复序列（LTR）的病毒和细胞转录因子之间的相互作用控制。对48例HIV-1蛋白酶（PR）基因携带不同亚型（9A、5C、3D、3F、21 G、2 H、3 J和2例未定义亚型）的临床标本进行了LTR区亚型分型和核苷酸LTR变异性分析。将来自每个HIV-1进化枝的LTR序列克隆到内切酶表达载体中，以确定在存在和不存在PMA刺激的情况下的基础和Tat诱导的转录活性。在LTR/PR区域鉴定了大量（37.8%）重组体。所有的HIV-1启动子都表现出较低的基础转录活性，但达特和PMA都能诱导这种活性。在响应达特和细胞活化的大多数HIV-1变体中，LTR活性相似。只有C亚型和CRF01_AE LTR的基础和诱导PMA转录活性高于HXB 2进化枝B启动子。与野生型启动子活性相比，在呈现G至A超突变的那些启动子中未发现基础或达特/PMA诱导的活性。在LTR内的一些重要的转录结合因子位点的G到A的超突变损害了病毒启动子的活性，降低了荧光素酶基因的体外病毒转录。
Transcriptional activation of HIV-1 gene expression is partially controlled by the interaction between viral and cellular transcription factors acting at HIV-1 long terminal repeat (LTR) sequences. HIV-1 subtyping at LTR region and nucleotide LTR variability from clinical samples in 48 subjects carrying different HIV-1 subtypes (9A, 5C, 3D, 3F, 21G, 2H, 3J and 2 undefined) at the protease (PR) gene, were performed. LTR sequences from each HIV-1 clade were cloned in luciferase-expression vectors to determine basal and Tat-induced transcriptional activities in the presence and absence of PMA stimulation. A high number (37.8%) of recombinants at LTR/PR regions were identified. All HIV-1 promoters presented low basal transcriptional activity that was nevertheless induced by Tat and PMA. LTR activity was similar across the majority of HIV-1 variants in response to Tat and cell activation. Only subtype C and CRF01_AE LTRs presented higher basal and induced-PMA transcription activities than HXB2 clade B promoter. No basal or Tat/PMA induced activity was found in those promoters presenting G to A hypermutation compared to the wild type promoter activities. G to A hypermutation at some important transcription binding-factor sites within LTR compromised the activity of the viral promoter, decreasing the in vitro viral transcription of the luciferase gene.
影响因子：
5.4
作者：
Montano, MA;Nixon, CP;Essex, M
通讯作者：
Essex, M
影响因子：
3.7
作者：
Yukl S;Pillai S;Li P;Chang K;Pasutti W;Ahlgren C;Havlir D;Strain M;Günthard H;Richman D;Rice AP;Daar E;Little S;Wong JK
通讯作者：
Wong JK