CELLULAR LATENCY IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED INDIVIDUALS WITH HIGH CD4 LEVELS CAN BE DETECTED BY THE PRESENCE OF PROMOTER-PROXIMAL TRANSCRIPTS
CELLULAR LATENCY IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED INDIVIDUALS WITH HIGH CD4 LEVELS CAN BE DETECTED BY THE PRESENCE OF PROMOTER-PROXIMAL TRANSCRIPTS
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DOI：
10.1073/pnas.91.9.3862
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发表时间：
1994-04-26
影响因子：
11.1
通讯作者：
EMERMAN, M
中科院分区：
文献类型：
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作者：
ADAMS, M;SHARMEEN, L;EMERMAN, M
我们在组织培养模型和HIV感染者中研究了人类免疫缺陷病毒1型(HIV-1)潜伏期的分子基础。我们发现，增加TAT的水平，而不是REV的水平，可以释放U1细胞中潜伏期的前病毒。TAT在这些细胞中的缺失表现为病毒启动子近端转录本的积累，而TAT的存在与病毒蛋白表达的增加和启动子远端转录本的增加有关。启动子近端转录本的存在也是人类潜伏期的一个标志。我们观察到大多数(10/11)无症状HIV感染者外周血单核细胞中的启动子-近端病毒转录物的存在。这些细胞在体外的激活和体内的病毒血症，与从启动子-近端转录到启动子-远端转录的转换相关。这些结果表明，HIV在体内的潜伏和复制之间的控制是在转录延伸水平上的。
We have investigated the molecular basis of human immunodeficiency virus type 1 (HIV-1) latency in a tissue culture model and in HIV-infected people. We show that increased levels of Tat, but not Rev, can release the proviruses from latency in U1 cells. The absence of Tat in these cells is manifested by the accumulation of promoter-proximal viral transcripts, whereas the presence of Tat correlates with increased expression of viral proteins and an increase in promoter-distal transcripts. The presence of promoter-proximal transcripts also serves as a marker for latency in humans. We observed the exclusive presence of promoter-proximal viral transcripts ire peripheral mononuclear cells from the majority (10/11) of asymptomatic HIV-infected individuals examined. Activation of these cells in vitro, and viremia in vivo, correlated with a switch from promoter-proximal transcription to promoter-distal transcription. These results suggest that the control between latency and replication of HIV in vivo is at the level of transcription elongation.