HDV在肝脏再生期间持续存在并通过细胞分裂进行扩增

StephenW

June 25, 2019
HDV Persists During Liver Regeneration and is Amplified Through Cell Division
Virginia Schad, PharmD
Hepatitis delta virus (HDV) persists during liver regeneration by transmitting HDV RNA to dividing cells even in the absence of hepatitis B virus (HBV) coinfection. Therefore the strong persistence capacities of HDV may explain why HDV clearance is difficult to achieve in HBV/HDV chronically infected patients, according to study results published in Gut.1

HDV infection is associated with severe liver disease and progression to cirrhosis, liver decompensation, hepatocellular carcinoma, and death.2 HBV plays an essential role as a helper virus for HDV transmission, and HDV infection usually occurs either upon simultaneous coinfection with HBV or as a superinfection in individuals already infected with HBV.1 It has been shown that HDV can persist for weeks in the absence of HBV and for months after liver transplantation, demonstrating the ability of HDV to persevere in quiescent hepatocytes. Therefore, researchers evaluated the impact of cell proliferation on HDV persistence in vitro and in vivo. In vitro, they infected genetically labeled human sodium taurocholate cotransporting polypeptide (hNTCP)-transduced human hepatoma (HepG2) cells with HBV/HDV and passaged every 7 days for 100 days in the presence of the entry inhibitor Myrcludex-B. In vivo, cell proliferation was triggered by transplanting primary human hepatocytes isolated from HBV/HDV-infected humanized mice into naïve mice. They found that HDV endures cell division in vitro and in vivo, and that cell division leads to the clonal expansion of HDV-positive cell clusters. This mechanism enables HDV to propagate among daughter cells even in the absence of HBV coinfection and despite the presence of the entry inhibitor Myrcludex-B.  


The researchers concluded that, “Taken together, the persistence capacity of HDV determined here and in previous studies highlights the importance to develop antivirals, which directly target HDV replication in combination with reinfection of human hepatocytes.”1


References
1. Giersch K, Bhadra OD, Volz T, et al. Hepatitis delta virus persists during liver regeneration and is amplified through cell division both in vitro and in vivo. Gut. 2019;68:150-157.

StephenW

2019年6月25日
HDV在肝脏再生期间持续存在并通过细胞分裂进行扩增
Virginia Schad，PharmD
即使在没有乙型肝炎病毒（HBV）合并感染的情况下，通过将HDV RNA传递给分裂细胞，肝脏再生期间肝炎病毒（HDV）仍然存在。因此，根据Gut.1发表的研究结果，HDV的强持久性能力可以解释为什么HBV / HDV慢性感染患者很难达到HDV清除率。

HDV感染与严重的肝脏疾病和进展为肝硬化，肝功能失代偿，肝细胞癌和死亡有关.2 HBV作为HDV传播的辅助病毒起着重要作用，HDV感染通常发生在与HBV同时共感染或作为已经感染HBV的个体的重复感染。已经表明，HDV可以在没有HBV的情况下持续数周并且在肝移植后持续数月，证明了HDV在静息肝细胞中持续存在的能力。因此，研究人员评估了细胞增殖对体外和体内HDV持久性的影响。在体外，他们用HBV / HDV感染遗传标记的人牛磺胆酸钠协同转运多肽（hNTCP）转导的人肝癌（HepG2）细胞，并在进入抑制剂Myrcludex-B存在下每7天传代100天。在体内，通过将分离自HBV / HDV感染的人源化小鼠的原代人肝细胞移植到幼稚小鼠中来触发细胞增殖。他们发现HDV在体外和体内都能维持细胞分裂，并且细胞分裂导致HDV阳性细胞簇的克隆扩增。即使在没有HBV共感染的情况下，尽管存在进入抑制剂Myrcludex-B，这种机制使得HDV能够在子细胞中传播。


研究人员得出结论：“总的来说，HDV在这里以及之前研究中确定的持久性能力强调了开发抗病毒药物的重要性，这些抗病毒药物直接针对HDV复制以及人肝细胞的再感染。”1


参考
1. Giersch K，Bhadra OD，Volz T，et al。肝脏再生期间肝炎病毒持续存在并且在体外和体内通过细胞分裂扩增。肠道。 2019; 68：150-157。