Transcription of the Herpes Simplex Virus Latency-Associated Transcript Promotes the Formation of Facultative Heterochromatin on Lytic Promoters
Transcription of the Herpes Simplex Virus Latency-Associated Transcript Promotes the Formation of Facultative Heterochromatin on Lytic Promoters
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DOI：
10.1128/jvi.00712-09
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发表时间：
2009-08-15
影响因子：
5.4
通讯作者：
Knipe, David M.
中科院分区：
文献类型：
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作者：
Cliffe, Anna R.;Garber, David A.;Knipe, David M.
病毒学中的一个重要问题是持续病毒(如疱疹病毒和人类免疫缺陷病毒)在特定类型的细胞中建立潜伏感染的机制(S)。就疱疹病毒而言，单纯疱疹病毒(HSV)感染上皮细胞会导致裂解性感染，而潜伏感染则建立在感觉神经元中。最近的研究表明，染色质结构在调节HSV和HIV的潜伏感染中具有重要作用。对于单纯疱疹病毒，我们以前已经证明，病毒潜伏期相关转录本(LAT)促进裂解基因沉默，并促进一个异染色质标记-组蛋白H3(H3K9me2)上赖氨酸9的二甲基化-与病毒裂解基因的关联。在这项研究中，我们通过检测与HSV潜伏基因组相关的组蛋白上的异染色质标记进一步定义了潜伏病毒染色质的结构。我们用H3K27me3检测到H3K9me2、H3K9me3和H3K27me3的修饰，这表明兼性异染色质在所有被测试的病毒启动子中表现出最高的丰度。未检测到与细胞着丝粒异染色质H4K20me3相关的修饰。在潜伏期内，在LAT区域内含有1.8KBP缺失的突变病毒显示兼性异染色质标记(H3K27me3)和H3K9me3的水平降低，而LAT启动子缺陷的突变病毒在H3K27me3中显示出特异性的减少。细胞中长的非编码RNA诱导兼性异染色质，本研究表明，病毒非编码RNA的转录也可以诱导兼性异染色质在潜伏期促进裂解基因沉默。
An important question in virology is the mechanism(s) by which persistent viruses such as the herpesviruses and human immunodeficiency virus (HIV) establish a latent infection in specific types of cells. In the case of herpesviruses, herpes simplex virus (HSV) infection of epithelial cells results in a lytic infection, whereas latent infection is established in sensory neurons. Recent studies have shown the importance of chromatin structure in the regulation of latent infection for both HSV and HIV. For HSV, we have shown previously that the viral latency-associated transcript (LAT) promotes lytic gene silencing and the association of one heterochromatin marker, dimethylation of lysine 9 on histone H3 (H3K9me2), with viral lytic genes. In this study, we further defined the structure of latent viral chromatin by examining the heterochromatin markers on histones associated with the HSV latent genome. We detected the H3K9me2, H3K9me3, and H3K27me3 modifications, with H3K27me3, which is indicative of facultative heterochromatin, exhibiting the highest enrichment on all viral promoters tested. A modification associated with cellular centromeric heterochromatin, H4K20me3, was not detected. A mutant virus containing a 1.8-kbp deletion within the LAT region showed reduced levels of the facultative heterochromatin marker (H3K27me3) along with H3K9me3 during latency, whereas a viral mutant defective for the LAT promoter showed a specific reduction in H3K27me3. Cellular long, noncoding RNAs induce facultative heterochromatin, and this study shows that transcription of a viral noncoding RNA can also induce facultative heterochromatin to promote lytic gene silencing during latency.