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空间转录组学揭示了在HBsAg损失的患者中,转录活性乙型肝炎病毒集成的程度较低

Xiaoqi Yu¹, Qiming Gong², Demin Yu¹

¹Department of Infectious Diseases, Research Laboratory of Clinical Virology, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China.

|November 15, 2023

概括

转录活跃的乙型肝炎病毒 (HBV) 集成发生在慢性感染中,即使在 HBsAg 损失后. 抗病毒治疗减少了这些整合,这表明早期干预可能会限制病毒传播和相关风险.

科学领域:

肝病学肝病学是一种肝病学.
病毒学病毒学
基因组学就是基因组学.

背景情况:

乙型肝炎病毒 (HBV) 融入宿主DNA是慢性感染的关键事件.
乙型肝炎病毒的整合有助于HBsAg的产生和肝癌发生.
不同感染阶段的HBV整合的空间分布和转录活性尚未完全理解.

研究的目的:

为了研究转录活性的HBV整合事件在肝脏组织中的空间分布.
分析慢性HBV感染不同阶段的HBV整合模式,包括HBsAg损失.
评估抗病毒治疗对HBV整合的影响.

主要方法:

18个慢性HBV感染肝脏活检的高分辨率空间转录.
对病毒-宿主模拟体的分析读取以确定HBV集成部位.
针对HBsAg和HBV核心抗原的免疫组织化学.
通过 qPCR 量化肝脏内共价封闭圆形DNA (cccDNA).

主要成果:

在所有患者的肝脏组织斑点中,检测到7.86%的转录活性HBV整合,包括那些HBsAg损失患者.
整合部位是随机分布的,发生在参与肝癌发生的宿主基因内 (例如,ALB,CLU,APOB).
与未接受治疗的患者相比,接受抗病毒治疗的患者的整合事件显著减少;ccccDNA水平与整合相关.

结论:

在慢性HBV感染中存在转录活性HBV整合,即使在HBsAg损失后也会持续存在.
抗病毒疗法与减少HBV整合有关,支持早期治疗,以潜在地限制病毒整合事件.

关键词:

慢性病毒性肝炎是一种慢性肝炎.乙型肝炎 B 型肝炎肝脏活检活检肝脏活检

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