Suv39H1 and HP1γ are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency
Suv39H1 and HP1γ are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency
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DOI：
10.1038/sj.emboj.7601517
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发表时间：
2007-01-24
期刊：
影响因子：
11.4
通讯作者：
Benkirane, Monsef
中科院分区：
文献类型：
--
作者：
du Chene, Isaure;Basyuk, Euguenia;Benkirane, Monsef
HIV-1基因表达是调节病毒复制速率的主要决定因素，从而影响艾滋病的进展。原发感染后，大多数感染细胞产生病毒。然而，一小部分人成为潜伏感染并构成病毒库。这种稳定的病毒库严重挑战了彻底根除病毒的希望。在这种情况下，确定参与转录潜伏期建立和病毒表达再激活的分子机制是至关重要的。我们发现Suv39H1， HP1 γ和组蛋白H3Lys9三甲基化在染色质介导的HIV-1基因表达的综合抑制中起主要作用。Suv39H1， HP1c和组蛋白H3Lys9三甲基化以转录依赖的方式与HIV-1可逆相关。最后，我们在不同的细胞模型中（包括来自HIV-1感染供体的pbmc）表明，在HP1c RNA干扰后，HIV-1可以实现再激活。
HIV-1 gene expression is the major determinant regulating the rate of virus replication and, consequently, AIDS progression. Following primary infection, most infected cells produce virus. However, a small population becomes latently infected and constitutes the viral reservoir. This stable viral reservoir seriously challenges the hope of complete viral eradication. Viewed in this context, it is critical to define the molecular mechanisms involved in the establishment of transcriptional latency and the reactivation of viral expression. We show that Suv39H1, HP1 gamma and histone H3Lys9 trimethylation play a major role in chromatin-mediated repression of integrated HIV-1 gene expression. Suv39H1, HP1c and histone H3Lys9 trimethylation are reversibly associated with HIV-1 in a transcription-dependent manner. Finally, we show in different cellular models, including PBMCs from HIV-1-infected donors, that HIV- 1 reactivation could be achieved after HP1c RNA interference.