人类乳头瘤病毒基因组在持续性病毒感染期间与主体活性染色体相关
bioRxiv : the preprint server for biology
|June 26, 2025
概括
人类乳头瘤病毒 (HPV) 与活跃的宿主细胞染色体结合,以维持基因表达. 这种与转录活跃区域的关联,容易发生DNA断裂,可能解释癌症中的病毒DNA集成.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 人类乳头瘤病毒 (HPV) 通过保持其基因组作为宿主角质细胞核内的小染色体来建立持久性感染.
- 了解病毒基因组与宿主染色体之间的相互作用对于阐明病毒持久性和病原性至关重要.
研究的目的:
- 研究HPV31基因组与宿主染色体结构的关联.
- 确定HPV31基因组定位是否与活跃的转录区域和DNA损伤部位相关.
主要方法:
- 利用染色体构造捕获技术,包括HiC和4C-seq,绘制HPV31基因组与宿主染色质的相互作用.
- 整合了ATAC-seq (开放色素) 和ChIP-seq (Brd4,H3K27ac超增强剂) 的数据,以定义宿主色素状态.
- 与公开可用的数据集相关的病毒基因组关联站点,用于双链DNA断裂 (dsDNA断裂) 和宫癌中的HPV整合站点.
主要成果:
- HPV31基因组首选与宿主染色体的转录活性"A"部分相关.
- 病毒基因组定位与开放的染色体区域 (ATAC-seq) 和超级增强剂 (Brd4,H3K27ac ChIP-seq) 强烈相关.
- 在宫癌和容易发生dDNA断裂的区域中,HPV31关联部位与已知的HPV整合部位有显著的重叠.
结论:
- HPV31基因组与宿主细胞转录中心结合,以确保感染期间的病毒基因表达活跃.
- 偏好转录活跃的,易破坏dDNA的染色体区域可能解释了在HPV相关癌症中观察到的高频率的病毒DNA整合.
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