HIV reproducibly establishes a latent infection after acute infection of T cells in vitro
HIV reproducibly establishes a latent infection after acute infection of T cells in vitro
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DOI：
10.1093/emboj/cdg188
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发表时间：
2003-04-15
期刊：
影响因子：
11.4
通讯作者：
Verdin, E
中科院分区：
文献类型：
--
作者：
Jordan, A;Bisgrove, D;Verdin, E
潜伏宿主的存在阻碍了从用抗逆转录病毒疗法成功治疗的受感染患者中根除人类免疫缺陷病毒（艾滋病毒）。整合后潜伏期的机制知之甚少，部分原因是缺乏体外模型。我们已经使用HIV逆转录病毒载体或表达绿色荧光蛋白的全长HIV基因组在体外感染T淋巴细胞系并高度富集潜伏感染的细胞。HIV潜伏期在急性感染期间可重复发生，尽管频率较低。克隆细胞系来源于潜伏群体表现出不可检测的基础表达，但可以转录激活后，佛波酯或肿瘤坏死因子α治疗。整合位点的直接测序表明，潜伏克隆经常包含HIV整合在异染色质中或接近α重复元件。这与其中整合在异染色质中或其附近是不利的生产性感染相反。这些观察结果表明，HIV可以可重复地建立一个潜伏感染的结果整合在异染色质或附近。
The presence of latent reservoirs has prevented the eradication of human immunodeficiency virus (HIV) from infected patients successfully treated with anti-retroviral therapy. The mechanism of postintegration latency is poorly understood, partly because of the lack of an in vitro model. We have used an HIV retroviral vector or a full-length HIV genome expressing green fluorescent protein to infect a T lymphocyte cell line in vitro and highly enrich for latently infected cells. HIV latency occurred reproducibly, albeit with low frequency, during an acute infection. Clonal cell lines derived from latent populations showed no detectable basal expression, but could be transcriptionally activated after treatment with phorbol esters or tumor necrosis factor alpha. Direct sequencing of integration sites demonstrated that latent clones frequently contain HIV integrated in or close to alphoid repeat elements in heterochromatin. This is in contrast to a productive infection where integration in or near heterochromatin is disfavored. These observations demonstrate that HIV can reproducibly establish a latent infection as a consequence of integration in or near heterochromatin.