乙肝病毒的进化和遗传变异性：对抗病毒药的预防，治疗和

StephenW

HBV evolution and genetic variability: impact on prevention, treatment and development of antivirals
Dieter Glebe  1 , Nora Goldmann  2 , Chris Lauber  3 , Stefan Seitz  4
Affiliations
Affiliations

    1
    Institute of Medical Virology, Justus Liebig University of Giessen, National Reference Centre for Hepatitis B Viruses and Hepatitis D Viruses, Schubertstr. 81, 35392, Giessen, Germany; German Center for Infection Research (DZIF), Partner Sites Giessen, Heidelberg, Hannover. Electronic address: [email protected].
    2
    Institute of Medical Virology, Justus Liebig University of Giessen, National Reference Centre for Hepatitis B Viruses and Hepatitis D Viruses, Schubertstr. 81, 35392, Giessen, Germany.
    3
    Division of Virus-Associated Carcinogenesis, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany; Research Group Computational Virology, Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Lnfection Research, a Joint Venture Between the Helmholtz Centre for Infection Research and the Hannover Medical School; Cluster of Excellence RESIST, Hannover Medical School, 30625, Hannover, Germany; German Center for Infection Research (DZIF), Partner Sites Giessen, Heidelberg, Hannover.
    4
    Division of Virus-Associated Carcinogenesis, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany; Department of Infectious Diseases, Molecular Virology, University of Heidelberg, 69120, Heidelberg, Germany; German Center for Infection Research (DZIF), Partner Sites Giessen, Heidelberg, Hannover. Electronic address: [email protected].

    PMID: 33166575 DOI: 10.1016/j.antiviral.2020.104973

Abstract

Hepatitis B virus (HBV) poses a major global health burden with 260 million people being chronically infected and 890,000 dying annually from complications in the course of the infection. HBV is a small enveloped virus with a reverse-transcribed DNA genome that infects hepatocytes and can cause acute and chronic infections of the liver. HBV is endemic in humans and apes representing the prototype member of the viral family Hepadnaviridae and can be divided into 10 genotypes. Hepadnaviruses have been found in all vertebrate classes and constitute an ancient viral family that descended from non-enveloped progenitors more than 360 million years ago. The de novo emergence of the envelope protein gene was accompanied with the liver-tropism and resulted in a tight virus-host association. The oldest HBV genomes so far have been isolated from human remains of the Bronze Age and the Neolithic (∼7,000 years before present). Despite the remarkable stability of the hepadnaviral genome over geological eras, HBV is able to rapidly evolve within an infected individual under pressure of the immune response or during antiviral treatment. Treatment with currently available antivirals blocking intracellular replication of HBV allows controlling of high viremia and improving liver health during long-term therapy of patients with chronic hepatitis B (CHB), but they are not sufficient to cure the disease. New therapy options that cover all HBV genotypes and emerging viral variants will have to be developed soon. In addition to the antiviral treatment of chronically infected patients, continued efforts to expand the global coverage of the currently available HBV vaccine will be one of the key factors for controlling the rising global spread of HBV. Certain improvements of the vaccine (e.g. inclusion of PreS domains) could counteract known problems such as low or no responsiveness of certain risk groups and waning anti-HBs titers leading to occult infections, especially with HBV genotypes E or F. But even with an optimal vaccine and a cure for hepatitis B, global eradication of HBV would be difficult to achieve because of an existing viral reservoir in primates and bats carrying closely related hepadnaviruses with zoonotic potential.

Keywords: HBV genotype diversity; HBV vaccination; antiviral treatment; hepadnaviruses; hepatitis B virus; virus evolution.

Copyright © 2020. Published by Elsevier B.V.

StephenW

乙肝病毒的进化和遗传变异性：对抗病毒药的预防，治疗和发展的影响
Dieter Glebe 1，Nora Goldmann 2，Chris Lauber 3，Stefan Seitz 4
隶属关系
隶属关系

    1个
    吉森贾斯图斯·利比希大学医学病毒学研究所，国家乙型肝炎病毒和丁型肝炎病毒参考中心，舒伯特。 81，35392，吉森，德国;德国感染研究中心（DZIF），合作伙伴站点吉森，汉诺威海德堡。电子地址：[email protected]。
    2
    吉森贾斯图斯·利比希大学医学病毒学研究所，国家乙型肝炎病毒和丁型肝炎病毒参考中心，舒伯特。 81，35392，吉森，德国。
    3
    德国海德堡69120，德国癌症研究中心（DKFZ）病毒相关癌变研究室； TWINCORE实验病毒研究所，计算病毒学研究小组，实验和临床感染研究中心，Helmholtz感染研究中心和汉诺威医学院之间的合资企业；汉诺威医学院RESIST杰出研究小组，德国汉诺威30625；德国感染研究中心（DZIF），合作伙伴站点吉森，汉诺威海德堡。
    4
    德国海德堡69120，德国癌症研究中心（DKFZ）病毒相关癌变研究室；海德堡大学分子病毒学传染病学系，德国海德堡69120；德国感染研究中心（DZIF），合作伙伴站点，吉森，汉诺威海德堡。电子地址：[email protected]。

    PMID：33166575 DOI：10.1016 / j.antiviral.2020.104973

抽象

乙型肝炎病毒（HBV）构成了全球主要的健康负担，有2.6亿人被慢性感染，并且在感染过程中每年因并发症而死亡890,000。 HBV是一种小包膜病毒，具有逆转录的DNA基因组，可感染肝细胞，并可引起肝脏的急性和慢性感染。 HBV是人类和猿类的地方性流行病，代表病毒科Hepadnaviridae的原型成员，可分为10个基因型。嗜肝DNA病毒已经在所有脊椎动物中发现，并且构成了一个古老的病毒家族，该家族起源于3.6亿多年前的非包膜祖细胞。包膜蛋白基因的从头出现伴随着肝向性并导致紧密的病毒-宿主关联。迄今为止，最古老的HBV基因组已从青铜时代和新石器时代（距今约7,000年）的人类遗体中分离出来。尽管在地质时代中嗜肝DNA病毒基因组具有显着的稳定性，但HBV仍能够在免疫反应的压力下或在抗病毒治疗期间在受感染的个体内迅速进化。在慢性乙型肝炎（CHB）患者的长期治疗过程中，使用目前可用的抗病毒剂阻断HBV在细胞内的复制，可以控制高病毒血症并改善肝脏健康，但不足以治愈该疾病。覆盖所有HBV基因型和新出现的病毒变体的新疗法必须尽快开发。除了对慢性感染患者进行抗病毒治疗外，继续努力扩大目前可用的HBV疫苗的全球覆盖范围将是控制HBV在全球范围内不断蔓延的关键因素之一。疫苗的某些改进（例如包含PreS结构域）可以解决已知问题，例如某些风险人群的反应性低或无反应，抗HBs滴度下降导致隐匿性感染，尤其是对于HBV基因型E或F。疫苗和乙型肝炎的治疗方法，由于在灵长类和蝙蝠中存在携带密切相关的具有人畜共患病潜力的肝炎病毒的蝙蝠中的病毒库，因此很难在全球范围内根除HBV。

关键词：HBV基因型多样性；乙肝疫苗接种；抗病毒治疗；嗜肝DNA病毒；乙型肝炎病毒;病毒进化。

版权所有©2020。由Elsevier B.V.发布。