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HTLV-1表达对宿主染色体3D结构和表达的影响

Hiroko Yaguchi¹, Anat Melamed¹, Saumya Ramanayake¹

¹Department of Infectious Diseases, Faculty of Medicine, Imperial College London, London, United Kingdom.

|March 1, 2024

概括

来自人类T淋巴细胞病毒1型 (HTLV-1) 的前病毒转录会导致宿主细胞转录的变化,但会破坏染色质循环. 当宿主转录减少时,这种干扰是可逆的.

科学领域:

病毒学病毒学
分子生物学分子生物学
基因组学就是基因组学.

背景情况:

人类T淋巴细胞病毒1型 (HTLV-1) 感染导致大量感染的T细胞克隆,每一个都有一个独特的前病毒集成部位.
HTLV-1前病毒集成可以导致横向宿主DNA的异常转录和涉及CTCF (CCCTC结合因子) 的异常染色质循环.

研究的目的:

确定HTLV-1对宿主基因组转录和染色质循环的前病毒性影响是否是由前病毒性存在或其转录引起的.
调查前病毒转录和宿主基因组改变之间的关系.

主要方法:

感染HTLV-1的T细胞克隆被根据前病毒加链表达 (阳性与阴性) 进行分类.
用RNA测序 (RNA-seq) 来量化宿主和前病毒转录.
使用定量染色体构造捕获 (q4C) 来评估染色体循环.

主要成果:

发现Proviral加链转录诱导异常转录和相邻宿主基因组中的拼接.
相反,前病毒转录抑制了与附近宿主DNA形成异常色素环的形成.
抑制proviral诱导的宿主转录允许在表达细胞中恢复色素环.

结论:

由HTLV-1前病毒表达驱动的异常宿主转录,是导致前病毒附近染色质循环的暂时和可逆性破坏的原因.
了解这种机制对于理解HTLV-1相关的病原体至关重要.

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