乙型肝炎病毒整合频率在人类基因组中的基因组建模

StephenW

Genomic modeling of hepatitis B virus integration frequency in the human genome

    Ondrej Podlaha,
    George Wu,
    Bryan Downie,
    Raghuraman Ramamurthy,
    Anuj Gaggar,
    Mani Subramanian,
    Zhishen Ye,
    Zhaoshi Jiang

PLOS

    Published: July 29, 2019
    https://doi.org/10.1371/journal.pone.0220376

  

Abstract

Hepatitis B infection is a world-wide public health burden causing serious liver complications. Previous studies suggest that hepatitis B integration into the human genome plays a crucial role in triggering oncogenic process and may also constitutively produce viral antigens. Despite the progress in HBV biology and sequencing technology, our fundamental understanding of how many hepatocytes in the liver actually carry viral integrations is still lacking. Herein we provide evidence that the HBV virus integrates with a lower-bound frequency of 0.84 per diploid genome in hepatitis B positive hepatocellular cancer patients. Moreover, we calculate that integrated viral DNA generates ~80% of the HBsAg transcripts in these patients. These results underscore the need to re-evaluate the clinical end-point and treatment strategies for chronic hepatitis B patients.

StephenW

乙型肝炎病毒整合频率在人类基因组中的基因组建模

    Ondrej Podlaha，
    乔治吴，
    布莱恩·唐尼，
    Raghuraman Ramamurthy，
    Anuj Gaggar，
    Mani Subramanian，
    智烨，
    赵绍江

PLOS

    发布时间：2019年7月29日
    https://doi.org/10.1371/journal.pone.0220376

  

抽象

乙型肝炎感染是世界范围的公共卫生负担，导致严重的肝脏并发症。以前的研究表明，乙型肝炎与人类基因组的整合在触发致癌过程中起着至关重要的作用，也可能组成性地产生病毒抗原。尽管HBV生物学和测序技术取得了进展，但我们仍然缺乏对肝脏中多少肝细胞实际携带病毒整合的基本认识。在这里，我们提供证据表明HBV病毒整合了乙型肝炎阳性肝细胞癌患者中每个二倍体基因组0.84的下限频率。此外，我们计算出整合的病毒DNA在这些患者中产生约80％的HBsAg转录物。这些结果强调了重新评估慢性乙型肝炎患者的临床终点和治疗策略的必要性。

StephenW

https://journals.plos.org/ploson ... ournal.pone.0220376

dxd2017

看了这个论文以及论文中的第27个引用，发现所有乙肝携带者都应该吃药，把ALT和DNA压制，5年 10年得肝癌的概率压缩到最低。
理论好像是肝癌和乙肝整合DNA有关系，吃药能减少整合，减少肝癌概率。