The impact of HTLV-1 on the cellular genome
The impact of HTLV-1 on the cellular genome
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DOI：
10.1016/j.coviro.2017.07.013
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发表时间：
2017-10-01
影响因子：
5.9
通讯作者：
Bangham, Charles R. M.
中科院分区：
文献类型：
--
作者：
Cook, Lucy;Melamed, Anat;Bangham, Charles R. M.
人类嗜T淋巴细胞病毒1型（HTLV-1）是成人T细胞白血病/淋巴瘤（ATL）的病原体，ATL是一种侵袭性CD 4 + T细胞恶性肿瘤。ATL中白血病发生的机制尚不完全清楚。此前，插入突变并未被认为与ATL的发病机制有关。然而，最近发现HTLV-1结合关键的染色质结构蛋白CTCF提出了这样的假设，即HTLV-1通过引起异常的染色质成环，使强HTLV-1启动子-增强子靠近位于距离整合的前病毒高达2 Mb的宿主基因，来解除宿主基因表达的调节。在这里，我们审查目前的意见，在ATL的肿瘤发生的机制，特别强调的本地和远程的影响HTLV-1对宿主基因组的结构和表达。
Human T-lymphotropic virus type-1 (HTLV-1) is the causative agent of adult T-cell leukaemia/lymphoma (ATL), an aggressive CD4+ T-cell malignancy. The mechanisms of leukaemogenesis in ATL are incompletely understood. Insertional mutagenesis has not previously been thought to contribute to the pathogenesis of ATL. However, the recent discovery that HTLV-1 binds the key chromatin architectural protein CTCF raises the hypothesis that HTLV-1 deregulates host gene expression by causing abnormal chromatin looping, bringing the strong HTLV-1 promoter-enhancer near to host genes that lie up to 2 Mb from the integrated provirus. Here we review current opinion on the mechanisms of oncogenesis in ATL, with particular emphasis on the local and distant impact of HTLV-1 on the structure and expression of the host genome.