由HBV驱动的宿主染色体可访问性变化会影响肝脏代谢途径,铁的稳态,并促进一个 preneoplastic 现型
Vincenzo Alfano1,2, Giuseppe Rubens Pascucci3,4, Giacomo Corleone5
1IHU EVEREST - Institut of Hepatology Lyon, UMR UCLB1 INSERM U1350 PaThLiv, 69004, Lyon, France.
概括
乙型肝炎病毒 (HBV) 感染会改变肝细胞染色质的可访问性和基因转录,影响新陈代谢和癌症途径. 这些表观遗传变化在慢性HBV和肝癌中持续存在,提供潜在的治疗点.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 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.
- 分子生物学分子生物学
背景情况:
- 乙型肝炎病毒 (HBV) 感染导致免疫功能障碍和病毒cccDNA持久性,使慢性HBV和治愈努力复杂化.
- 乙型肝炎病毒对肝脏转录组和染色质可访问性的直接影响仍然不完全理解.
- 核细胞组织和染色体重塑对于真核细胞的转录激活至关重要.
研究的目的:
- 为了研究HBV感染对宿主细胞染色质可访问性的影响.
- 分析肝脏中由HBV感染引起的早期转录性变化.
- 了解HBV感染的长期表观遗传后果.
主要方法:
- 检测转移酶可访问的染色体,然后使用高通量测序 (ATAC-seq) 来评估染色体的可访问性.
- 用RNA测序 (RNA-seq) 来分析转录的个人资料.
- 这些方法应用于感染HBV的初级人类肝细胞 (PHHs).
主要成果:
- 随着时间的推移,HBV感染导致核细胞组织和染色质可访问性的动态变化.
- ATAC-seq和RNA-seq数据的整合揭示了HBV对肝脂肪酸,胆酸,铁代谢和癌症途径的影响.
- 铁吸收基因的升级增加了细胞铁含量,铁化抑制了ccccDNA转录和病毒复制.
- 在慢性HBV患者和与HBV相关的HCC中,由HBV诱导的染色质和转录变化作为表观遗传痕持续存在,基本上独立于病毒复制水平.
结论:
- 乙型肝炎病毒感染显著重塑宿主细胞染色质格局,并改变转录程序,特别是在肝脏代谢和与癌症相关的途径.
- 感染早期HBV对铁代谢的重新连接增强了病毒复制.
- 与癌症相关的基因的调节可能会促进亲新生代表型,在与HBV相关的肝细胞癌 (HCC) 中持续存在.
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