Arya S K, Gallo R C
Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1988 Dec;85(24):9753-7. doi: 10.1073/pnas.85.24.9753.
The long terminal repeats (LTRs) of the human immunodeficiency virus type 2 (HIV-2) and a related simian immunodeficiency virus (SIVmac) contain cis-acting positive regulatory elements upstream and the major transactivator gene (tat) response element and a possible negative regulatory element downstream of the transcriptional initiation site. The tat response element of HIV-2 and of SIVmac was more complex than that of HIV-1. Two structurally similar subelements within the HIV-2 tat response element could be identified. Both of these subelements were required for optimal transactivation by the HIV-2 tat gene product. Either of these subelements, however, was sufficient for transactivation by the HIV-1 tat gene product. These observations provide an explanation for the poor transactivation of HIV-1 LTR-directed gene expression by the HIV-2 tat gene product since the HIV-1 LTR contains an analog of only one of the HIV-2 subelements. The HIV-2 tat gene product also affected the function of the upstream elements, including enhancer activity. The response of these cis elements of HIV-2 to transactivation by HIV-2/SIVmac and HIV-1 tat gene differed somewhat in virus-infected and tat gene transfected cells, probably related to the differences in the effective concentration of the tat gene products and/or other viral or cellular factors. The steady-state levels of HIV-2 LTR-linked gene transcripts were much higher in the presence of HIV-2, SIVmac, and HIV-1 tat genes than in their absence, suggesting transcriptional modulation as a mechanism for tat gene function.
人类免疫缺陷病毒2型（HIV-2）和一种相关的猴免疫缺陷病毒（SIVmac）的长末端重复序列（LTRs）在转录起始位点上游含有顺式作用阳性调节元件、主要反式激活基因（tat）反应元件以及下游一个可能的阴性调节元件。HIV-2和SIVmac的tat反应元件比HIV-1的更为复杂。在HIV-2 tat反应元件内可鉴定出两个结构相似的亚元件。这两个亚元件都是HIV-2 tat基因产物实现最佳反式激活所必需的。然而，这两个亚元件中的任何一个对于HIV-1 tat基因产物的反式激活都是足够的。这些观察结果解释了HIV-2 tat基因产物对HIV-1 LTR指导的基因表达反式激活能力较差的原因，因为HIV-1 LTR仅包含HIV-2亚元件之一的类似物。HIV-2 tat基因产物还影响上游元件的功能，包括增强子活性。HIV-2的这些顺式元件对HIV-2/SIVmac和HIV-1 tat基因反式激活的反应在病毒感染细胞和tat基因转染细胞中有所不同，这可能与tat基因产物的有效浓度以及/或其他病毒或细胞因子的差异有关。在存在HIV-2、SIVmac和HIV-1 tat基因的情况下，HIV-2 LTR相关基因转录本的稳态水平比不存在这些基因时高得多，这表明转录调节是tat基因发挥功能的一种机制。
