Herpesviral latency-associated transcript gene promotes assembly of heterochromatin on viral lytic-gene promoters in latent infection
Herpesviral latency-associated transcript gene promotes assembly of heterochromatin on viral lytic-gene promoters in latent infection
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DOI：
10.1073/pnas.0505850102
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发表时间：
2005-11-01
影响因子：
11.1
通讯作者：
Knipe, DM
中科院分区：
文献类型：
--
作者：
Wang, QY;Zhou, CH;Knipe, DM
单纯疱疹病毒（HSV）持续存在于其人类宿主中，并通过在感觉神经元中经历潜伏感染来逃避免疫反应，从而可以周期性地重新激活。HSV在生产性（“裂解性”）感染期间表达> 80个基因产物，但在潜伏感染期间仅潜伏相关转录物（LAT）基因以丰富水平表达。LAT基因已显示抑制感觉神经元中的裂解基因表达。在这项研究中，我们使用染色质免疫沉淀显示，HSV裂解基因启动子成为复杂的修改历史与异染色质在建立潜伏感染的过程中。比较LAT阴性和LAT阳性病毒的实验表明，LAT基因编码的功能增加了病毒裂解基因启动子上组蛋白H3或异染色质的二甲基赖氨酸9形式的量，并减少了组蛋白H3的二甲基赖氨酸4形式的量，这是活性染色质的一部分。因此，HSV，特别是HSV LAT基因，可以操纵细胞组蛋白修饰机制以抑制其裂解基因表达，并有助于其基因组在感觉神经元中以静止形式持续存在。
Herpes simplex virus (HSV) persists in its human host and evades the immune response by undergoing a latent infection in sensory neurons, from which it can reactivate periodically. HSV expresses > 80 gene products during productive ("lytic") infection, but only the latency-associated transcript (LAT) gene is expressed at abundant levels during latent infection. The LAT gene has been shown to repress lytic-gene expression in sensory neurons. In this study, we use chromatin immunoprecipitation to show that HSV lytic gene promoters become complexed with modified histories associated with heterochromatin during the course of establishment of latent infection. Experiments comparing LAT-negative and LAT-positive viruses show that a function encoded by the LAT gene increases the amount of dimethyl lysine 9 form of histone H3 or heterochromatin and reduces the amount of dimethyl lysine 4 form of histone H3, a part of active chromatin, on viral lytic-gene promoters. Thus, HSV, and in particular the HSV LAT gene, may manipulate the cellular histone modification machinery to repress its lytic-gene expression and contribute to the persistence of its genome in a quiescent form in sensory neurons.