Differences in transcriptional enhancers of HIV-1 and HIV-2. Response to T cell activation signals.
Differences in transcriptional enhancers of HIV-1 and HIV-2. Response to T cell activation signals.
复制标题
DOI：
10.4049/jimmunol.145.12.4348
复制
发表时间：
1990-12
影响因子：
4.4
通讯作者：
S. Tong-Starksen;T. M. Welsh;B. Peterlin
中科院分区：
文献类型：
--
作者：
S. Tong-Starksen;T. M. Welsh;B. Peterlin
T细胞活化导致高水平的HIV复制，并且被认为是导致从潜伏性病毒感染转化为活性病毒感染的一种机制。在HIV-1中，应答这些信号事件的序列存在于长末端重复序列（LTR）中，并包含转录增强子，其含有两个保守的核因子κ B（NF κ B）结合位点。在第二种艾滋病逆转录病毒HIV-2中的相应区域含有保守的和不同的NF κ B结合位点。我们证明了HIV-1 LTR比HIV-2 LTR对T细胞活化信号的反应更好。不仅当HIV-1或HIV-2增强子置于异源启动子上游时，而且当这些增强子在其各自的LTR之间转换时，对T细胞活化的应答中的这些质的差异也会重现。在电泳迁移率变动分析中，NF κ B B结合HIV-1转录增强子中的两个保守位点，并且仅结合HIV-2转录增强子中的单个保守位点。激活蛋白3与HIV-2中的分歧位点结合，而不是NF kappa B。总之，HIV-1和HIV-2受T细胞活化信号的差异调节，这种差异可能是HIV-2感染比HIV-1感染观察到的病毒潜伏期更长的原因。
T cell activation results in high levels of HIV replication and is thought to be one mechanism leading to the conversion from latent to active viral infection. In HIV-1, the sequences that respond to these signaling events are found in the long terminal repeat (LTR) and comprise the transcriptional enhancer, which contains two conserved binding sites for the nuclear factor kappa B (NF kappa B). The corresponding region in the second AIDS retrovirus, HIV-2, contains a conserved and a divergent NF kappa B binding site. We demonstrate that the HIV-1 LTR responds better than the HIV-2 LTR to T cell activation signals. These qualitative differences in the response to T cell activation are reproduced not only when HIV-1 or HIV-2 enhancers are placed upstream of a heterologous promoter but also when these enhancers are switched between their respective LTR. In electrophoretic mobility shift assays, NF kappa B binds to both conserved sites in the HIV-1 transcriptional enhancer and only to the single conserved site in the HIV-2 transcriptional enhancer. Instead of NF kappa B, the activator protein 3 binds to the divergent site in HIV-2. In conclusion, HIV-1 and HIV-2 are differentially regulated by T cell activation signals, and this difference may account for the longer period of viral latency observed with HIV-2 than with HIV-1 infection.